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Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Glassblowers handcrafting today's high quality pieces are still doing it pretty much the same way like their ancestors. That means also working with a lot of fire (and subsequent unavoidable burns). In heats which are so common lately, they therefore need to adhere to strict drinking regime, which includes to drink 6 litres of water during a shift. They also have allowed low-proof beer for better hydration effect, as it have additionally electrolytes, carbohydrates, minerals, photo-nutrients and fermentation process have positive effect on these ingredients by promoting increased bioavailability and enzymatic activity.
From Wikipedia, the free encyclopedia
C-123 Provider
Role Military transport aircraft
Manufacturer Chase Aircraft
Fairchild Aircraft
Designer Michael Stroukoff
First flight 14 October 1949
Introduction 1956
Retired United States Air Force c. 1980[citation needed]
Status Active with flying clubs
Primary users United States Air Force (historical)
United States Coast Guard (historical)
Republic of Vietnam Air Force (historical)
Produced 1949–1970
Number built 307
Developed from Chase XCG-20
Variants Chase XC-123A
Stroukoff YC-134
The Fairchild C-123 Provider is an American military transport aircraft designed by Chase Aircraft and then built by Fairchild Aircraft for the U.S. Air Force. In addition to its USAF service, which included later service with the Air Force Reserve and the Air National Guard, it also went on to serve most notably with the U.S. Coast Guard and various air forces in Southeast Asia. During the War in Vietnam, the C-123 was used to deliver supplies, to evacuate the wounded, and also used to spray Agent Orange.
The C-123 Provider was designed originally as an assault glider aircraft for the United States Air Force (USAF) by Chase Aircraft as the XCG-20 (Chase designation MS-8 Avitruc)[1] Two powered variants of the XCG-20 were developed during the early 1950s, as the XC-123 and XC-123A. The only difference between the two was the type of engines used. The XC-123 used two Pratt & Whitney R-2800-23 air-cooled radial piston engines, while the XC-123A was fitted with four General Electric J47-GE-11 turbojets, in two pods.[2] The XC-123A also has the distinction, while only experimental, of being the USAF first jet-powered military transport.[3] While the piston-powered XC-123 was initially well-regarded for tactical transport for its ruggedness and reliability, and its ability to operate from short and unimproved airstrips, the turbojet-powered XC-123A – designed for high-speed transport between USAF bases for critical parts and personnel – was found unable to operate from short and rough airstrips. There was also no practical speed advantage due to the wing and fuselage design, and a drastic reduction in range. Only the one turbojet-powered test and evaluation version was built.[citation needed]
By 1953, Henry J. Kaiser purchased a majority share in Chase Aircraft, feeling that after having completed C-119s for Fairchild under contract, he could take control of the impending C-123 contract. Two airframes were completed at Kaiser's Willow Run factory in Ypsilanti, Michigan, before a pricing scandal that led to Kaiser's being told that no further contracts with him would be honored. The C-123 contract was put up for bid, and the two completed airframes scrapped. The contract was finally awarded to Fairchild Engine and Airplane, who assumed production of the former Chase C-123B, a refined version of the XC-123.[4] Before turning production over to Fairchild, Chase originally named their C-123B the AVITRUC but it never stuck.[5]
Operational history
The first recipients of C-123 aircraft were USAF transport units, soon followed by the U.S. Coast Guard (USCG) which used the aircraft for search and rescue (SAR) missions, and even the U.S. Air Force Demonstration Team, the "Thunderbirds," used C-123s for a time as a logistics support aircraft for transporting the team's ground crews and equipment. The type would also be widely exported under various U.S. military assistance programs, directly from USAF stocks. A C-123 was used to transport President John F. Kennedy's limousine during his November, 1963, Texas tour.
USAF C-123Bs in the 1950s.
The C-123 was nearly ignored by the USAF for service in Vietnam, but a political rivalry with the U.S. Army and the Army's use of the CV-2 Caribou and later pre-production order for the de Havilland Canada C-8 Buffalo, led to a decision to deploy C-123s there. To compete with the well-performing CV-2, the USAF and Fairchild furthered development on the C-123 to allow it to do similar work on short runways. This additional development increased the utility of the aircraft and its variants to allow it to perform a number of unique tasks, including the HC-123B which operated with the USCG fitted with additional radar equipment for search and rescue missions through 1971, and the C-123J which was fitted with retractable skis for operations in Greenland and Alaska on compacted snow runways.
By 1962, the C-123K variant aircraft was evaluated for operations in Southeast Asia and their stellar performance led the Air Force to upgrade 180 of the C-123B aircraft to the new C-123K standard, which featured auxiliary jet pods underneath the wings, and anti-skid brakes. In 1968, the aircraft helped resupply troops in Khe Sanh, Vietnam, during a three-month siege by North Vietnam.[1]
A number of C-123s were configured as VIP transports, including General William Westmoreland's White Whale. The C-123 also gained notoriety for its use in "Operation Ranch Hand" defoliation operations in Vietnam. Oddly enough, the USAF had officially chosen not to procure the VC-123C VIP transport, opting instead for the Convair VC-131D.
The first C-123s to reach South Vietnam were part of the USAF's Special Aerial Spray Flight, as part of Operation Ranch Hand tasked with defoliating the jungle in order to deny rebels their traditional hiding places.[6] These aircraft began their operations at the end of 1961. Aircraft fitted with spraying equipment were given the U prefix as a role modifier, with the most common types being the UC-123B and the UC-123K. Aircraft configured for this use were the last to see military service, in the control of outbreaks of insect-borne disease. The C-123 was also used as "jump aircraft" for U.S. Army Airborne students located at Lawson Army Airfield, Fort Benning, Georgia in the late 1970s and early 1980s. This aircraft was used in conjunction with the Lockheed C-130 Hercules and Lockheed C-141 Starlifter.
In 1958, the U.S. Coast Guard received its first HC-123B, followed by seven more in 1961. Installation of a dome on the nose of the aircraft accommodated a large radar allowing the plane to meet the requirements for search and rescue and long range flight over water. The Coast Guard manned the aircraft with a crew of five: two officers serving as the pilot and copilot, augmented by an enlisted flight mechanic, an enlisted navigator, and an enlisted loadmaster. The HC-123B's role in the Coast Guard was slowly replaced by the longer-ranged Coast Guard HC-130 aircraft during the 1960s and 1970s as those newer airframes came on line.[7][unreliable source?]
With the end of the Vietnam War, remaining C-123Ks and UC-123Ks were transferred to tactical airlift units of the Air Force Reserve (AFRES) and the Air National Guard (ANG) that were operationally-gained by Tactical Air Command (TAC) before 1975 and Military Airlift Command (MAC) after 1975.[8]
The 302nd Tactical Airlift Wing at Rickenbacker AFB (later Rickenbacker ANGB), Ohio, flew the last UC-123Ks Providers in operational service before being converted to the Lockheed C-130 Hercules. Known as the Special Spray Flight, these aircraft were used to control insect-borne diseases, with missions to Alaska, South America, and Guam being among the humanitarian missions performed by this Air Force Reserve unit.[9]
The final examples of the C-123 in active U.S. military service were retired from the Air Force Reserve and Air National Guard in the early 1980s. Some airframes were transferred to the Federal Aviation Administration (FAA) for test and evaluation programs while others were transferred to the U.S. Department of Agriculture (USDA) for miscellaneous programs. These aircraft were also retired by the end of the 1990s.
In 1954, the YC-123D, formerly the XC-123A prototype, flew in its modified state after being converted by Stroukoff Aircraft. While the most obvious change from the original XC-123A was the switch of engines (to two 3,500 hp (2,600 kW) Wright Turbo Compound R3350-89A radial engines, turning four-blade, thirteen foot Aeroproducts constant-speed fully feathering propellers), the YC-123D also had a boundary layer control system fitted. This system directs air from the engines at high speed over the top of the wing, making the wing act as if the aircraft is flying at a higher airspeed. As a result, the YC-123D had a greatly reduced takeoff and landing distance. Compared to the C-123B, the YC-123D could land in 755 feet instead of 1,200, and takeoff with only 850 ft of runway instead of 1,950, with a 50,000 lb total weight.
In 1955, Stroukoff, under contract from the USAF, produced a single YC-123E, designed to be able to take off from any surface, and also equipped with BLC. The new aircraft also featured Stroukoff's Pantobase system, combining a ski system with a sealed fuselage and wing mounted floats, while retaining its normal landing gear. The skis worked both on snow and water, and the system effectively allowed the aircraft to land on water, land, snow or ice.
In 1956, the USAF awarded a contract to Fairchild to design an improved version of the C-123 under the designation C-136, but the contract was cancelled before the aircraft was built.[10]
At much the same time, the YC-123H was under development, the product of a Fairchild modification program started in 1956 and completed in 1957.[citation needed] A "Jet Augmentation Program" for existing C-123Bs had been initiated in 1955 at the behest of the USAF, and in the YC-123H contract the USAF expanded it to allow the mounting of two pod-mounted General Electric J85 turbojets.
In 1979, the Royal Thai government, seeking to extend the life of their C-123 fleet, placed a contract with the Mancro Aircraft Company, supported by the USAF, to convert a single C-123B to turboprop powerplants.[citation needed] Allison T56-A-7 turboprops were used and by the time the aircraft, dubbed C-123T, was complete it had new "wet" wings, an auxiliary power unit (APU) to assist with power movement of the control surfaces, and a heating system for the cargo compartments that also fed a new de-icing system.[citation needed] Budgetary restrictions forced the Thai government to abandon the program in 1981, and with a lack of interested parties development of the C-123T stopped.[citation needed] However, it concluded the life of the C-123 by making it the only aircraft type to operate under jet, piston, and turboprop engine power, and as a glider, during its history.[citation needed][N 1]
The C-123T has recently been revived by a joint venture between the US-based Fleetwings Aircraft Company and the South African company Elmer Group. In 2010, they announced a project to initially remanufacture old airframes for African customers and, where there was demand, to build new aircraft. The airframes would be fitted with new turboprop Rolls-Royce T56-A-15 engines, a glass cockpit and other enhancements. The proposed C-123T would have had a 25,000 lb payload capability, and a take-off run of just over 1,000 ft at 50,000 lb MTOW. Possible applications included maritime patrol, search and rescue, and even use as a gunship, while roll-on packages have already been developed for mid-air refueling and agricultural applications.[11]
During the Vietnam War, some C-123s were modified for specialized roles. Most of these modifications were on a one- or two-aircraft level. Only the usage of C-123s as "flare ships" to illuminate targets for fixed wing gunships such as the AC-47 and AC-119G were more numerous. These aircraft operating under the call-sign Candle were flown by the USAF's 14th Special Operations Wing.
US Air Force NC-123K "permanent test" model used over the Ho Chi Minh Trail. It was outfitted with a forward looking infrared system, low light level television, a laser rangefinder, and cluster bomb dispensers.
A single C-123B was tested as a possible replacement for the Candle aircraft, with its rear loading ramp removed and replaced with a large box with 28 large lights. The aircraft could continuously light a two-mile circle from an altitude of 12,000 ft. This aircraft, under the provisional designation NC-123B, was dropped because the lights fixed to the aircraft made it far easier for enemy gunners to track compared to the earlier flare ships.
The "Candle" aircraft had an extended life when several UC-123Ks were transferred to Nakhon Phanom Royal Thai Air Force Base in Thailand. During that period, it was used as a flare ship as well as a forward air control (FAC) aircraft. The flare duties were generally used for troops in contact (TIC) while the FAC mission directed air strikes in Laos over the Ho Chi Minh trail.
Another NC-123B was used as a radio relay aircraft over the Ho Chi Minh trail, with equipment to read the signals from various sensors on the ground designed to pick up enemy truck activity.
Two C-123K aircraft modified in September 1965 under Project Black Spot.[12] The Black Spot aircraft were to fit under the "self-contained night attack capability" that was Operation Shed Light's primary focus and E-Systems of Greenville, Texas, was contracted to complete the modifications. These aircraft featured a variety of new sensors including Low Light Level TV (LLLTV), Forward Looking Infrared (FLIR), and a laser rangefinder.[13] The aircraft looked radically different visibly from its transport brethren, as the new equipment required lengthening the nose by over 50 inches.[14] The aircraft also featured an armament system designed to carry BLU-3/B (using the ADU-253/B adapter) or BLU-26/B (using the ADU-272/B adapter) bomblets, or CBU-68/B cluster bombs.[15][16]
The two aircraft, AF Serial Numbers 54-0691 and 54-0698, were first designated NC-123K in 1968 and then redesignated AC-123K in 1969.[N 2] These NC/AC-123Ks were first deployed operationally at Osan AB, South Korea, between August and October 1968, and flying in support of operations against North Korean infiltrators approaching by boat. The operations in Korea met with a certain level of success and as a result the NC/AC-123Ks were transferred to South Vietnam in November 1968. The aircraft operated there until January 1969, when they were redeployed to Ubon RTAB, Thailand. The two aircraft were then returned to the United States to Hurlburt Field, Florida, in May 1969, where a second round of training occurred. Four crews attended a ground school in Greenville, Texas, and returned to Hurlburt where they flew the aircraft for the first time.
The fate of the aircraft is still unclear. Sources have missions terminating in early July 1970 and the aircraft flying to the Military Aircraft Storage and Disposition Center (MASDC) "boneyard" at Davis-Monthan AFB, Arizona, where they were returned to C-123K standard, then returned to South Vietnam still wearing their camouflage and black undersides for transport duty.[14] However, the official history states that combat operations ceased on 11 May 1969, with no mention of the second deployment.[12] While the second deployment is mentioned in associated documentation, the only dates are of the arrival in Thailand and there is no information as to when they departed or where their destination was.[17]
Main article: Operation Shed Light
Covert operations
Southeast Asia
In 1962, the CIA acquired five C-123Bs from USAF for Air America to be used in Laos and Vietnam, and another 5 C-123Bs to be used by Republic of China Air Force (Taiwan) top secret 34th Squadron, a Black Ops units called the "Black Bat", as Flight B section (Flight A section was the two P2V-2U/RB-69A). The five Taiwan C-123Bs were sent to Lockheed Skunk Works for modifications as covert insertion aircraft with "smart" air-to-air jammer, BSTR system to jam the radars of ground anti-aircraft guns, also added a defensive operator's station to operate the jammers on board, with extra fuel in underwing tanks, with 36 Taiwanese crew finished training courses at Pope AFB by November 1962.
The five ROCAF/Taiwan/CIA C-123Bs would be used over North Vietnam as low level and nighttime covert airdrop aircraft, under the South Star II agreement, under the guise of Taiwan's national airline, China Airlines, which had "cover story" of operating Vietnamese Air Transport (VIAT) in South Vietnam, that was formerly operated by Air America. The secret outfit was based in Saigon, but would fly out of Da Nang for airdrop missions going into North Vietnam, with some missions lasting 14 hours.
On 1 February 1964, the overall control of South Star II was transferred from CIA to Studies and Observations Group (SOG), as part of U.S. Military Assistance Command Vietnam (MACV) in Saigon. The outfit was redesignated as Det. 1 of USAF's 75th Troop Carrier Squadron (TCS), but within SOG it was known as the First Flight Detachment (FFD).
In May 1964, under "Project Duck Hook", six more C-123s received extensive modifications by Lockheed Air Service at Ontario, California, equipped with ATIR and BSTR ECM packages, ASN-25 Doppler navigation system, APN-153 terrain-following radar, a console station for radio operator, new HF radio and other radios. These aircraft were issued to the secret Taiwanese Black Bat unit operating in South Vietnam. In October 1964, MACV, CIA and ROCAF/Taiwan signed the South Star III agreement to continue the operation in Vietnam. The six "Duck Hook" C-123Bs were based at Nha Trang Air Base, north of Cam Ranh Bay, officially designated as USAF Det. 12 of 1131 Special Activities Squadron.
The "Duck Hook" C-123Bs were updated with RDR-10 weather radar and ARN-131 homing receiver in 1966 in order to perform missions over the Ho Chi Minh trail. All C-123Bs were converted to C-123Ks in 1968, with two wing-mounted turbjets, plus an ECM upgrade with APR-25 radar warning receiver and ALE-1 chaff dispenser. Project "Duck Hook" designation was ultimately changed to "Heavy Hook". The Det. 12 of 1131 Special Activities Squadron unit at Nha Trang received an outstanding unit award from the USAF, for flying 4,000 classified combat and combat support missions from June 1966 to May 1968.
In May 1970, C-123Ks from the "Black Bats" supported the secret U.S. military incursion into Cambodia. In October 1970, flights into Laos began. In March 1972, the SOG was deactivated, and the Southern Star operation ended with four surviving C-123Ks returned to Taiwan. On 1 March 1973, 34th "Black Bat" Squadron of ROCAF/Taiwan was disbanded.[18]
Central America
On 5 October 1986, a Corporate Air Services C-123 Provider (HPF821, previously N4410F and USAF 54-679, (c/n 20128))[19] departed San Salvador-Ilopango Airport in El Salvador loaded with 70 AK-47 rifles and 100,000 rounds of ammunition, rocket grenades and other supplies. It flew along the coastline of Nicaragua and entered Nicaraguan airspace near the border with Costa Rica. Nearing San Carlos, the plane descended to 2,500 feet while preparing to drop off its cargo to Contra fighters.
While conducting the drop, the C-123 was shot down by a Sandinista soldier, using a SA-7 Grail. CIA pilots Wallace "Buzz" Sawyer and William Cooper were killed in the crash. Loadmaster Eugene Hasenfus parachuted to safety and was taken prisoner. He was later released in December 1986.[20] The Fairchild C-123 that was shot down in Nicaragua remains there. Its sister ship, also a Fairchild C-123 that was purchased by the CIA at the same time as the first one, was then left abandoned at San Jose International Airport for a time and then was purchased for $3,000 and disassembled into 7 pieces and transported via boat to Quepos, Costa Rica and then reassembled and is now the center piece of a beachside cocktail lounge just up the road from Manual Antonio national park.
Agent Orange controversy
In 2011, a retired Air Force officer, Major Wesley T. Carter, filed a complaint with the Air Force Inspector General alleging that the Air Force knew that UC-123Ks used for spraying Agent Orange in Vietnam remained contaminated and that the Air Force had failed to properly inform subsequent flight crews of the risks following their transfer to the Air Force Reserve at the end of the Vietnam War. In his complaint, Major Carter contends that the Air Force has known since 1994 that the aircraft were contaminated with the defoliant; he cites the fact that when a former C-123 was being prepared for a permanent static display that workers had to use HAZMAT suits and respirators. Additionally, it is asserted that when the aircraft was tested by the Air Force, it contained high levels of the known carcinogen polychlorinated dibenzodioxin, studies since confirmed by the Oregon Health Sciences University and Columbia University's Mailman School of Public Health.[citation needed]
The aircraft which were flown from 1972–1982, were assigned to the Air Force Reserve after their service in Vietnam, and used for normal cargo and aeromedical evacuation missions. Air crews accumulated hundreds of flight hours aboard several contaminated aircraft that were often flown with the windows open due to the smell and eye irritation. Memos surfaced showing that Air Force JAG officers recommended keeping the toxicity information, "...within official channels." Further, Major Carter located Air Force reports of dioxin-contaminated aircraft sold abroad, and of one used at the Robins AFB, Georgia Museum of Aviation with public access to the contaminated surfaces of the aircraft. In 2010, due to concerns about dioxin contamination, the Air Force took the unusual step of shredding all the remaining surplus C-123K/UC-123K aircraft and melting the scraps into ingots for disposal.[21]
On 9 June 2011, the Secretary of the U.S. Air Force's Inspector General rejected Carter's complaints, and in a subsequent message explained, "Unfortunately, we do not have the ability to identify or notify the individuals in the categories you mention" when asked if the military would alert the aircrews regarding their exposure to dioxin. On 18 June 2011, the veterans' complaint was accepted with the Department of Defense Inspector General, adding the request that the UC-123K aircraft themselves be designated by the Secretary of Defense as "Agent Orange Exposure Sites".[22]
In December 2011, the U.S. Department of Veterans Affairs posted two notices of its decision that, while the post-Vietnam aircraft "may" have been contaminated, the aircrews were "unlikely" to have suffered exposure to dioxin. In an unusual response, the U.S. Center for Toxic Substance and Disease Registry quickly countered the VA position on 25 January 2012 with a statement by their Deputy Director concluding that aircrews and maintenance personnel most likely were exposed well beyond military and government surface-wipe screening levels.[23]
In November 2011, the USAF School of Aerospace Medicine began its own investigation into lingering C-123 contamination. In April 2012, the USAF School of Aerospace Medicine released its review of the C-123 Agent Orange exposure issue and reported their researchers were unable to determine the degree of exposure, if any, which aircrews may have had aboard the contaminated aircraft in the period 1972–1982. Their report was, in turn, challenged by university-based experts Richard Clapp and Jeannie Stellman, both of whom continue to assert contaminated aircraft exposed the aircrews as well as aerial port and maintenance veterans. As of August 2012, the U.S. Department of Veterans Affairs has denied service-connection (the linking of a veteran's illness to military service) to every application for medical benefits.
In September 2012, Thomas Murphy, Director of VA Compensation Services, wrote that TCDD (the well-known toxic component of Agent Orange) has not been shown to cause harm to humans in his denial of one veteran's application. On 25 November 2012, a committee of scientists and physicians, chaired by Jeanne Stellman, informed the VA Under Secretary for Benefits Allison Hickey that the VA's scientific conclusions regarding the C-123 situation were ill-founded and called on the VA to involve outside experts in a re-evaluation. In a subsequent telecon, Deputy Chief Consultant Dr. T. Walters informed veterans no C-123 exposure claims would be permitted to be approved, the VA forming a denial basis around redefining the word "exposure" to include bioavailability. No bioavailability equals no exposure, and thus no exposure claims permitted and indeed, since veterans began learning of the contamination of the C-123 fleet, no exposure claims have been approved other than via appeal to the VA Board of Correction.
Veterans have cited the 8 May 2001 Federal Register, page 23166, and the 31 August 2010 Federal Register, page 5320 5, each of which state:carried the VA statement: '"Finally, we wish to make clear that the presumptions of service connection provided by this rule will apply to any veteran who was exposed during service to the herbicides used in Vietnam, even if exposure occurred outside of Vietnam. A veteran who is not presumed to have been exposed to herbicides, but who is shown by evidence to have been exposed, is eligible for the presumption of service connection for the diseases listed in § 3.309(e)."
In August 2013, the Department of Veteran's Affairs approved the disability claim of Lt. Col. Paul Bailey. This is the first time the VA has recognized a crew member's claim related to Agent Orange exposure while flying planes after the Vietnam War.[24] The legal questions attracted significant attention from veterans' advocates, and the National Veterans Legal Services Project and the Yale Law School Veterans Legal Clinic published a comprehensive legal analysis. Exposure was confirmed as the single requirement upon veterans to prove for meeting Agent Orange disability claim requirements, and Yale Law detailed the exhaustive list of proofs establishing the veterans' exposure over the decade of post-Vietnam service of the former Agent Orange aircraft. Besides the legal analysis, Yale's purpose was that their finding be useful for all C-123 veterans in submitting disability claims to the Department of Veterans Affairs.
In February 2014, a team of scientists headed by Dr. Jeanne Stellman and including Dr. Peter Lurker, Dr. Fred Berman and Dr. Richard Clapp published a pivotal scientific article in Environmental Research Titled Post Vietnam Military Herbicide Exposures in UC-123K Agent Orange Aircraft". The authors challenged both VA and USAF testing methods and earlier conclusions that the C-123K fleet was toxicologically harmless. Their research established that veterans had far greater, and more harmful, exposures than earlier estimated, and that the veterans' TCDD exposures exceeded any published safety standard. The authors noted:
Air Force Reserves flew about 34 dioxin-contaminated transport aircraft, 1971–1982.
VA denies benefits, claiming dioxin was bound in “non-available dried residue".
We used limited available sampling data and 3 methods to model dioxin exposure.
Estimated dermal–oral exposure exceeded US EPA standards for certain personnel.
Estimated airborne contamination exceeded the only available standard (Germany).
In response to developing scientific challenges to its position refusing C-123 veterans' exposure claims, on March 10, 2014 VA began revising their web pages to include reference to the submission of a special C-123 study project for the Institute of Medicine. First promised to the C-123 veterans in 2012, this study directs IOM to consider medical implications of their exposures. The results were published by the IOM on 9 January 2015, solidly confirming the post-Vietnam veterans' herbicide exposures, and faulting the 2012 USAF C-123 Consultative Letter which had relied on incorrect application of a formula in determining toxicity. Under Secretary Hickey assured veterans that VA would abide by the IOM findings, and VA immediately formed a committee to address its next step as C-123 veterans are brought into the VA health care system.
Variants
Chase XCG-20
Two prototype all-metal troop transport gliders built by Chase Aircraft, later designated the XG-20, one became the XC-123, the other the XC-123A.
Chase XC-123
Former XG-20 fitted with two 2,200 hp R-2800-23 engines.
Chase XC-123A
Former XG-20 fitted with four J47-GE-11 turbojets in pairs (of the type used by the B-36 and B-47[25]) under wings.[2][26]
C-123B
Production model based on the XC-123 with two 2300 hp R-2800-99W engines with accommodation for 61 troops or 50 stretchers, five built by Chase and 302 build by Fairchild Aircraft.
UC-123B
C-123Bs modified for defoliation and crop destruction duties.
VC-123C
Executive transport version of the jet-powered XC-123A, not built.
Stroukoff YC-123D
One aircraft built by Stroukoff with boundary layer control system for improved STOL performance.
Stroukoff YC-123E
One aircraft built by Stroukoff with modified fin and rudder, modified fuselage bottom (called Pantobase) and pontoon floats to allow operation from water, sand, snow or ice.
YC-123H
Prototype with wide track undercarriage and two underwing J85 booster engines.
C-123J
C-123B with two wing tip mounted Fairchild J44-R-3 booster engines, 10 converted.
C-123K
C-123Bs with two underwing J85 booster engines and larger wheels, 183 converted.
AC-123K/NC-123K
Two C-123Bs converted for armed nighttime surveillance with special sensors.
C-123L
Proposed STOL variant with T-64 turboprop engines and a wide-track, large-wheel main landing gear – not proceeded with. (Fairchild Model M-541 Tactical Airlift Transport)[27]
C-123T
Proposed upgrade for Royal Thai Air Force C-123Bs including installation of turboprop engines; cancelled after one prototype due to budgetary reasons.
HC-123B
USCG search and rescue variant
UC-123K
C-123Ks converted for Ranch Hand defoliation missions, 34 converted.
VC-123K
One C-123K converted as personal transport for General Westmoreland's use in Vietnam.
Stroukoff YC-134
One aircraft built by Stroukoff, as C-123B but fitted with boundary layer control system, tailplane endplates, redesigned landing gear with tandem main wheels. Later designated YC-134A when fitted with Pantobase landing gear.
YC-136
Proposed improved variant; cancelled before any aircraft built.
Operators
Brazil
Brazilian Air Force – two resold to VARIG
Cambodia
Khmer Air Force
Republic of China (Taiwan)
Republic of China Air Force
34th "Black Bat Squadron", 1962 to 1973[18]
4 C-123K, retired in 1981
El Salvador
Air Force of El Salvador
Laos
Royal Lao Air Force
Lao People's Liberation Army Air Force
Philippines
Philippine Air Force
Saudi Arabia
Royal Saudi Air Force
A South Korean C-123K in 1989.
South Korea
Republic of Korea Air Force
South Vietnam
Republic of Vietnam Air Force
Thailand
Royal Thai Air Force
United States
United States Air Force
United States Coast Guard
Venezuela
Venezuelan Air Force
Accidents and incidents
Crash site of the C-123 from Con Air, Mount Healy, Denali National Park, Alaska
10 October 1958: A C-123B Provider, AF Ser. No. 55-452', en route from Hill AFB, Utah to McChord AFB, Washington, with five USAF Thunderbirds flight crew and 14 maintenance personnel, flew through a flock of birds and crashed into a hillside six miles east of Payette, Idaho, just before 1830, killing all on board.[28] This accident remains the worst loss-of-life in the Thunderbirds team history.
11 December 1965: En route to Tuy Hoa Air Base, a USAF C-123 hit some trees on top of a ridge, causing it to enter a spin and crash. Four American officers and 81 South Vietnamese paratroopers were killed.[29]
24 January 1966: A C-123K operated by the USAF (Registration 54-0702) lost power and crashed after take-off from An Khe, en route to Bong Son. The aircraft was transporting troops taking part in Operation Masher. The crew of four and 42 members of the 1st Air Cavalry Division were killed.[30]
27 November 1970: A C-123K #55-4574 on approach to Nha Trang Air Base in poor visibility crashed into terrain killing six U.S. crew and 73 South Vietnamese.[31][32]
29 November 1970: A C-123K #54-0649 on approach to Cam Ranh Air Base crashed into terrain killing 42 onboard.[33]
27 December 1971: A C-123K enroute from Udorn Royal Thai Air Force Base, to Xieng Lom located in northwestern Laos, was reportedly shot down by anti-aircraft fire approximately 35 km east northeast of Xieng Lom resulting in the loss of four crew members. In October, 1997, a Joint Task Force (JTF 98-IL) located the crash site. After three excavations (2017-2018) the remains of three crew members were identified.[34]
16 October 1980: A UC-123K of the Ohio Air National Guard crashed shortly after take off en route home from Fort Sill, Oklahoma to Rickenbacker ANGB, Ohio.[35] Four crew members died on impact, the fifth died later.[36]
6 February 1982: A South Korean Air Force C-123 crashed into a volcano while on approach to Jeju International Airport, killing all 53 people on board.[37]
1 June 1982: A South Korean Air Force C-123 crashed into Mt. Choenggye, killing all 53 people on board.[38]
1 August 2010: The aircraft used for flying scenes in the movie Con Air, C-123K, former AF Ser. No. 54-0709, FAA registration N709RR (cn: 20158), crashed in Denali National Park while performing a cargo flight for All West Freight. All three crew members died.[39]
Surviving Aircraft
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A C-123K on display at Air Mobility Command Museum at Dover AFB.
C-123B displays at the Royal Thai Air Force Museum
C-123K display at the Museum of Aviation, Robins AFB
54-0555 – Royal Thai Air Force Museum, Don Muang AFB.[40]
54-0576 – Jesada Technik Museum, Thailand, C-123K (aircraft used in Operation Dumbo Drop)
54-0580 – Pima Air and Space Museum (adjacent to Davis-Monthan AFB), Tucson, Arizona, C-123(B)K (On loan from US Forest Service)[41]
54-0593 – Wilford Hall Medical Center, Lackland AFB, Texas[42]
54-0604 – Dyess AFB, Texas, C-123K (on loan from NMUSAF)
54-0609 – Fort Bragg, North Carolina, 82nd Airborne Division War Memorial Museum, C-123K
54-0610 – Hill Aerospace Museum, Hill AFB, Utah, C-123K (on loan from NMUSAF).[43]
54-0612 – March ARB, California, March Field Air Museum, C-123K (on loan from NMUSAF).[44]
54-0624 – Benito Ebuen AFB, Mactan Island, Philippines, PAF
54-0629 – McGuire AFB, Trenton, New Jersey[45]
54-0633 – Robins AFB, Georgia, Museum of Aviation, C-123B (on loan from NMUSAF).[46]
54-0658 – Dover AFB, Delaware, Air Mobility Command Museum, C-123K (on loan from NMUSAF).[47]
54-0663 – El Avion restaurant in Hotel Costa Verde, Costa Rica has the twin of the CIA-operated aircraft downed by the Sandinista forces over Nicaragua in 1986. The aircraft has been converted into a bar.[48]
54-0664 – Air Heritage Museum in Beaver Falls, Pennsylvania; this museum's C-123K, nicknamed "ThunderPig," is operational and available for air shows.[49]
54-0668 – Lackland AFB, Texas, C-123K (on loan from NMUSAF)
54-0669 – Pope AAF (former Pope AFB), North Carolina, Pope Air Park, C-123K (painted as AF Ser. No. 54-0372) (on loan from NMUSAF)
54-0674 – Air America Foundation, Inc., owns a C-123K, housed at Space Coast Regional Airport, Titusville, Florida.[50]
54-0683 – Air Force Flight Test Museum, California, sitting alongside a C-119 Flying Boxcar on an unused runway south of the air base. This aircraft was auctioned off in early 2016.[51]
54-0687 – Muan International Airport, South Korea
54-0695 – Mid-America Transportation and Aviation Museum, Sioux City, Iowa.[52]
55-4505 – Pima Air and Space Museum (adjacent to Davis-Monthan AFB), Tucson, Arizona, C-123B (on loan from NMUSAF, former Ranch Hand aircraft)
55-4507 – Travis AFB, California, Travis Air Museum, C-123K (on loan from NMUSAF).[53]
55-4509 – Jeju Aerospace Museum, South Korea
55-4512 – Castle Airport (former Castle AFB), California, Castle Air Museum, C-123K (on loan from NMUSAF).[54]
55-4533 – Hurlburt Field, Florida, Hurlburt Field Memorial Air Park, C-123K (on loan from NMUSAF)
55-4558 – Museum of Alaska Transport and Industry, Wasilla Airport, Alaska
55-4567 – Little Rock AFB, Arkansas, C-123K (on loan from NMUSAF)
56-4360 – Jinpo maritime Theme park, Gunsan, South Korea
56-4361 – Wendover Airport, Wendover, Utah[55]
56-4362 – National Museum of the United States Air Force, Wright-Patterson AFB, Ohio, C-123K (Patches, former Ranch Hand aircraft).[56]
56-4375 – Ilopango International Airport, El Salvador, C-123K with serial FAS-122 is on static display, this is one of the original aircraft provided by the United States Air Force to the Salvadorean Air Force during the Salvadoran Civil War. When was in service with the USAF, it was used, by General William Westmoreland, during the Vietnam War conflict, back then was called "The White Whale" VC-123B 56-4375 (AF 56-4375) which were used as VIP transports.
56-4386/9 – War Memorial of Korea, Seoul, South Korea
56-4395 – Former Kulis ANGB, Anchorage, Alaska, C-123J (on loan from NMUSAF)
UNKNOWN – SpringHill Camps, Evart, Michigan. This C-123K has been repurposed as a camp cabin for year-round use.[57]
UNKNOWN – Caltex gas station, Bang Whua subdistrict, Bang Pakong district, Chachoengsao province, Thailand. Retired C-123B of the Royal Thai Air Force converted into a cafe called "Coffee 123" or more popularly known by the locals as the airplane cafe.[58]
Several other examples of C-123s remain in an active flying status, operated by private owners in the United States or by various air forces worldwide.[59][60]
Specifications (C-123K Provider)
Data from The Observer's Book of Basic Aircraft: Military (dimensions)[61] and Jane's All The World's Aircraft 1969–70 (weights and performance)[62]
General characteristics
Crew: 4
Capacity: 60 passengers, 50 litters, or 24,000 pounds (11,000 kg) of cargo
Length: 76 ft, 3 in (23.25 m)
Wingspan: 110 ft, 0 in (33.53 m)
Height: 34 ft, 1 in (10.39 m)
Wing area: 1,223 ft² (113.7 m²)
Empty weight: 35,366 lb (16,042 kg)
Max. takeoff weight: 60,000 lb (27,215 kg)
Powerplant:
2 × General Electric J85-GE-17 turbojets, 2,850 lbf (13 kN) each
2 × Pratt & Whitney R-2800-99W "Double Wasp" 18-cylinder radial engines, 2,500 hp (1,865 kW) each
Performance
Maximum speed: 228 mph (198 knots, 367 km/h) at 10,000 ft (3,050 m)
Cruise speed: 173 mph (150 knots, 278 km/h)
Stall speed: 95 mph (83 knots, 152 km/h)
Range: 1,035 mi (899 nm, 1,666 km) with max payload
Ferry range: 3,280 mi (2,852 nmi, 5,280 km)
Service ceiling: 21,100 ft (6,430 m) "OEO" (One engine failed)
Rate of climb: 1,220 ft/min (6.2 m/s) "OEO" (One engine failed)
Fairchild C-123 used for static and taxi scenes in Con Air (1997), at Wendover Airfield, c. 2011
Notable appearances in media
Main article: Aircraft in fiction: C-123 Provider
A C-123K (54-709), N709RR (since destroyed in a crash in 2010) was prominently featured in the action film Con Air (1997); other C-123s appeared in Air America (1990), Outbreak (1995), Operation Dumbo Drop (1995) and American Made (2017), none of which were used in Operation Ranch Hand.[63][64] A C-123 was seen in the last episode of Season 5 of Nash Bridges where it was used by criminals and was shot down just after takeoff when Nash used a shoulder fired surface to air missile.
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn. Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States, Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70% to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn. Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel. When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
ORNAMENTAL AND OTHER USES
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
The Carrotinians - Exhibit Catalog. Item 444444+or-2 (aka 7)
The above is a detail of a larger work originally found on the side of a barn in Iowa. Extensive study by sciadophytographists determined that it is definitely composed of ancient carrotenoidal phycobiliproteins on rotting wood. Further study established that it is the work of a nephew of Daucus the 3th, Bloomery "l'œil" Xanthophyll.
Due to an abundance of carotenoid bioavailability, Bloomery (aka Trompe) brimmed with élan vital and had numerous careers simultaneously. He was a sgraffitologist,
a scagliolalogist, a marmorinologist and a spatolatologist. He was also an amateur suminagashiologist and is sometimes considered as the inventor of shabby chic. Soon after he met and married his wife, Myrna Adele, he opened a sucessful furnace factory.
Bloomery survived until a ripe old age. His hand-written autobiography (still under study) was, most fortunately, found after he had been composted. It was titled 'S Marbleous and would surely have meant a much earlier harvest for Bloomery had it been discovered by the Carrotian Expunging Committee.
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn.[5] Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States,[30] Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70%[57] to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn.[91] Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel.[120] When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
Ornamental and other uses
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
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Testosterone
The chemical structure of testosterone.
A ball-and-stick model of testosterone.
Names
IUPAC name
17β-Hydroxyandrost-4-en-3-one
Systematic IUPAC name
(8R,9S,10R,13S,14S,17S)-17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
Other names
Androst-4-en-17β-ol-3-one
Identifiers
CAS Number
58-22-0 ☑
3D model (JSmol)
Interactive image
ChEBI
CHEBI:17347 ☑
ChEMBL
ChEMBL386630 ☑
ChemSpider
5791 ☑
DrugBank
DB00624 ☑
ECHA InfoCard100.000.336
KEGG
D00075 ☑
PubChem CID
6013
UNII
3XMK78S47O ☑
InChI[show]
SMILES[show]
Properties
Chemical formula
C19H28O2
Molar mass288.431 g·mol−1
Melting point155 °C
Pharmacology
ATC code
G03BA03 (WHO)
License data
EU EMA: by INN
Routes of
administration
Transdermal (gel, cream, solution, patch), by mouth (as testosterone undecanoate), in the cheek, intranasal (gel), intramuscular injection (as esters), subcutaneous pellets
Pharmacokinetics:
Bioavailability
Oral: very low (due to extensive first pass metabolism)
Protein binding
97.0–99.5% (to SHBG and albumin)[1]
Metabolism
Liver (mainly reduction and conjugation)
Biological half-life
2–4 hours[citation needed]
Excretion
Urine (90%), feces (6%)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Testosterone is the primary male sex hormone and an anabolic steroid. In male humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair.[2] In addition, testosterone is involved in health and well-being,[3] and the prevention of osteoporosis.[4] Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss.
Testosterone is a steroid from the androstane class containing a keto and hydroxyl groups at the three and seventeen positions respectively. It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites.[5] It exerts its action through binding to and activation of the androgen receptor.[5] In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females.[6] As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men.[7][8] Females are also more sensitive to the hormone.[9]
In addition to its role as a natural hormone, testosterone is used as a medication, for instance in the treatment of low testosterone levels in men and breast cancer in women.[10] Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in athletes.
Contents
1Biological effects
1.1Before birth
1.2Early infancy
1.3Before puberty
1.4Pubertal
1.5Adult
1.6Aggression and criminality
1.7Brain
2Medical use
3Biological activity
3.1Steroid hormone activity
3.2Neurosteroid activity
4Biochemistry
4.1Biosynthesis
4.2Distribution
4.3Metabolism
4.4Levels
5Measurement
6History
7Other animals
8See also
9References
10Further reading
Biological effects[edit]
In general, androgens such as testosterone promote protein synthesis and thus growth of tissues with androgen receptors.[11] Testosterone can be described as having virilising and anabolic effects (though these categorical descriptions are somewhat arbitrary, as there is a great deal of mutual overlap between them).[12]
Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.
Androgenic effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in the fetus, and after birth (usually at puberty) a deepening of the voice, growth of facial hair (such as the beard) and axillary (underarm) hair. Many of these fall into the category of male secondary sex characteristics.
Testosterone effects can also be classified by the age of usual occurrence. For postnatal effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone.
Before birth[edit]
Effects before birth are divided into two categories, classified in relation to the stages of development.
The first period occurs between 4 and 6 weeks of the gestation. Examples include genital virilisation such as midline fusion, phallic urethra, scrotal thinning and rugation, and phallic enlargement; although the role of testosterone is far smaller than that of dihydrotestosterone. There is also development of the prostate gland and seminal vesicles.
During the second trimester, androgen level is associated with sex formation.[13] This period affects the femininization or masculinization of the fetus and can be a better predictor of feminine or masculine behaviours such as sex typed behaviour than an adult's own levels. A mother's testosterone level during pregnancy is correlated with her daughter's sex-typical behavior as an adult, and the correlation is even stronger than with the daughter's own adult testosterone level.[14]
Early infancy[edit]
Early infancy androgen effects are the least understood. In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–7 months of age.[15][16] The function of this rise in humans is unknown. It has been theorized that brain masculinization is occurring since no significant changes have been identified in other parts of the body.[17] The male brain is masculinized by the aromatization of testosterone into estrogen, which crosses the blood–brain barrier and enters the male brain, whereas female fetuses have α-fetoprotein, which binds the estrogen so that female brains are not affected.[18]
Before puberty[edit]
Before puberty effects of rising androgen levels occur in both boys and girls. These include adult-type body odor, increased oiliness of skin and hair, acne, pubarche (appearance of pubic hair), axillary hair (armpit hair), growth spurt, accelerated bone maturation, and facial hair.[19]
Pubertal[edit]
Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of free testosterone in the blood. The effects include:[19][20]
Growth of spermatogenic tissue in testicles, male fertility, penis or clitoris enlargement, increased libido and frequency of erection or clitoral engorgement occurs. Growth of jaw, brow, chin, and nose and remodeling of facial bone contours, in conjunction with human growth hormone occurs.[21] Completion of bone maturation and termination of growth. This occurs indirectly via estradiol metabolites and hence more gradually in men than women. Increased muscle strength and mass, shoulders become broader and rib cage expands, deepening of voice, growth of the Adam's apple. Enlargement of sebaceous glands. This might cause acne, subcutaneous fat in face decreases. Pubic hair extends to thighs and up toward umbilicus, development of facial hair (sideburns, beard, moustache), loss of scalp hair (androgenetic alopecia), increase in chest hair, periareolar hair, perianal hair, leg hair, armpit hair.
Adult[edit]
Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia. It regulates acute HPA (hypothalamic–pituitary–adrenal axis) response under dominance challenge.[22] Androgen including testosterone enhances muscle growth. Testosterone also regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans.[23][24]
Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Some of these effects may decline as testosterone levels might decrease in the later decades of adult life.[25]
Health risks[edit]
Testosterone does not appear to increase the risk of developing prostate cancer. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer.[26][27][28]
Conflicting results have been obtained concerning the importance of testosterone in maintaining cardiovascular health.[29][30] Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters that are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.[31]
High androgen levels are associated with menstrual cycle irregularities in both clinical populations and healthy women.[32]
Sexual arousal[edit]
See also: Hormones and sexual arousal
When testosterone and endorphins in ejaculated semen meet the cervical wall after sexual intercourse, females receive a spike in testosterone, endorphin, and oxytocin levels, and males after orgasm during copulation experience an increase in endorphins and a marked increase in oxytocin levels. This adds to the hospitable physiological environment in the female internal reproductive tract for conceiving, and later for nurturing the conceptus in the pre-embryonic stages, and stimulates feelings of love, desire, and paternal care in the male (this is the only time male oxytocin levels rival a female's).[citation needed]
Testosterone levels follow a nyctohemeral rhythm that peaks early each day, regardless of sexual activity.[33]
There are positive correlations between positive orgasm experience in women and testosterone levels where relaxation was a key perception of the experience. There is no correlation between testosterone and men's perceptions of their orgasm experience, and also no correlation between higher testosterone levels and greater sexual assertiveness in either sex.[34]
Sexual arousal and masturbation in women produce small increases in testosterone concentrations.[35] The plasma levels of various steroids significantly increase after masturbation in men and the testosterone levels correlate to those levels.[36]
Mammalian studies[edit]
Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviors (copulation, partner preference, etc.) resumed, but not when given low amounts of the same hormone. Therefore, these mammals may provide a model for studying clinical populations among humans suffering from sexual arousal deficits such as hypoactive sexual desire disorder.[37]
In every mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a novel female. The reflexive testosterone increases in male mice is related to the male's initial level of sexual arousal.[38]
In non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females.[39] Some research has also indicated that if testosterone is eliminated in an adult male human or other adult male primate's system, its sexual motivation decreases, but there is no corresponding decrease in ability to engage in sexual activity (mounting, ejaculating, etc.).[39]
In accordance with sperm competition theory, testosterone levels are shown to increase as a response to previously neutral stimuli when conditioned to become sexual in male rats.[40] This reaction engages penile reflexes (such as erection and ejaculation) that aid in sperm competition when more than one male is present in mating encounters, allowing for more production of successful sperm and a higher chance of reproduction.
Males[edit]
In men, higher levels of testosterone are associated with periods of sexual activity.[41][42]
Men who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films.[43] Men who watch sexually explicit films also report increased motivation, competitiveness, and decreased exhaustion.[44] A link has also been found between relaxation following sexual arousal and testosterone levels.[45]
Men's levels of testosterone, a hormone known to affect men's mating behaviour, changes depending on whether they are exposed to an ovulating or nonovulating woman's body odour. Men who are exposed to scents of ovulating women maintained a stable testosterone level that was higher than the testosterone level of men exposed to nonovulation cues. Testosterone levels and sexual arousal in men are heavily aware of hormone cycles in females.[46] This may be linked to the ovulatory shift hypothesis,[47] where males are adapted to respond to the ovulation cycles of females by sensing when they are most fertile and whereby females look for preferred male mates when they are the most fertile; both actions may be driven by hormones.
Females[edit]
Androgens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal.[48] Women's level of testosterone is higher when measured pre-intercourse vs pre-cuddling, as well as post-intercourse vs post-cuddling.[49] There is a time lag effect when testosterone is administered, on genital arousal in women. In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors.[50]
When females have a higher baseline level of testosterone, they have higher increases in sexual arousal levels but smaller increases in testosterone, indicating a ceiling effect on testosterone levels in females. Sexual thoughts also change the level of testosterone but not level of cortisol in the female body, and hormonal contraceptives may affect the variation in testosterone response to sexual thoughts.[51]
Testosterone may prove to be an effective treatment in female sexual arousal disorders,[52] and is available as a dermal patch. There is no FDA approved androgen preparation for the treatment of androgen insufficiency; however, it has been used off-label to treat low libido and sexual dysfunction in older women. Testosterone may be a treatment for postmenopausal women as long as they are effectively estrogenized.[52]
Romantic relationships[edit]
Falling in love decreases men's testosterone levels while increasing women's testosterone levels. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes.[53] However, it is suggested that after the "honeymoon phase" ends—about four years into a relationship—this change in testosterone levels is no longer apparent.[53] Men who produce less testosterone are more likely to be in a relationship[54] or married,[55] and men who produce more testosterone are more likely to divorce;[55] however, causality cannot be determined in this correlation. Marriage or commitment could cause a decrease in testosterone levels.[56] Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts.[57] Married men who engage in bond-maintenance activities such as spending the day with their spouse/and or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities are more relevant to changes in testosterone levels.[58]
Men who produce more testosterone are more likely to engage in extramarital sex.[55] Testosterone levels do not rely on physical presence of a partner; testosterone levels of men engaging in same-city and long-distance relationships are similar.[54] Physical presence may be required for women who are in relationships for the testosterone–partner interaction, where same-city partnered women have lower testosterone levels than long-distance partnered women.[59]
Fatherhood[edit]
Fatherhood decreases testosterone levels in men, suggesting that the emotions and behavior tied to decreased testosterone promote paternal care. In humans and other species that utilize allomaternal care, paternal investment in offspring is beneficial to said offspring's survival because it allows the parental dyad to raise multiple children simultaneously. This increases the reproductive fitness of the parents, because their offspring are more likely to survive and reproduce. Paternal care increases offspring survival due to increased access to higher quality food and reduced physical and immunological threats.[60] This is particularly beneficial for humans since offspring are dependent on parents for extended periods of time and mothers have relatively short inter-birth intervals.[61] While extent of paternal care varies between cultures, higher investment in direct child care has been seen to be correlated with lower average testosterone levels as well as temporary fluctuations.[62] For instance, fluctuation in testosterone levels when a child is in distress has been found to be indicative of fathering styles. If a father's testosterone levels decrease in response to hearing their baby cry, it is an indication of empathizing with the baby. This is associated with increased nurturing behavior and better outcomes for the infant.[63]
Motivation[edit]
Testosterone levels play a major role in risk-taking during financial decisions.[64][65]
Aggression and criminality [edit]
See also: Aggression § Testosterone, and Biosocial criminology
Most studies support a link between adult criminality and testosterone, although the relationship is modest if examined separately for each sex. Nearly all studies of juvenile delinquency and testosterone are not significant. Most studies have also found testosterone to be associated with behaviors or personality traits linked with criminality such as antisocial behavior and alcoholism. Many studies have also been done on the relationship between more general aggressive behavior/feelings and testosterone. About half the studies have found a relationship and about half no relationship.[66]
Testosterone is only one of many factors that influence aggression and the effects of previous experience and environmental stimuli have been found to correlate more strongly. A few studies indicate that the testosterone derivative estradiol (one form of estrogen) might play an important role in male aggression.[66][67][68][69] Studies have also found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus.[70]
The sexual hormone can encourage fair behavior. For the study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. The rules allowed both fair and unfair offers. The negotiating partner could subsequently accept or decline the offer. The fairer the offer, the less probable a refusal by the negotiating partner. If no agreement was reached, neither party earned anything. Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. Two later studies have empirically confirmed these results.[71][72][73] However men with high testosterone were significantly 27% less generous in an ultimatum game.[74] The Annual NY Academy of Sciences has also found anabolic steroid use which increase testosterone to be higher in teenagers, and this was associated with increased violence.[75] Studies have also found administered testosterone to increase verbal aggression and anger in some participants.[76]
Testosterone is significantly correlated with aggression and competitive behaviour and is directly facilitated by the latter. There are two theories on the role of testosterone in aggression and competition.[77] The first one is the challenge hypothesis which states that testosterone would increase during puberty thus facilitating reproductive and competitive behaviour which would include aggression.[77] Thus it is the challenge of competition among males of the species that facilitates aggression and violence.[77] Studies conducted have found direct correlation between testosterone and dominance especially among the most violent criminals in prison who had the highest testosterone levels.[77] The same research also found fathers (those outside competitive environments) had the lowest testosterone levels compared to other males.[77]
The second theory is similar and is known as "evolutionary neuroandrogenic (ENA) theory of male aggression".[78][79] Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible.[78] The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low digit ratio as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game.[80] Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.[81][82][83][84][85]
The rise in testosterone levels during competition predicted aggression in males but not in females.[86] Subjects who interacted with hand guns and an experimental game showed rise in testosterone and aggression.[87] Natural selection might have evolved males to be more sensitive to competitive and status challenge situations and that the interacting roles of testosterone are the essential ingredient for aggressive behaviour in these situations.[88] Testosterone produces aggression by activating subcortical areas in the brain, which may also be inhibited or suppressed by social norms or familial situations while still manifesting in diverse intensities and ways through thoughts, anger, verbal aggression, competition, dominance and physical violence.[89] Testosterone mediates attraction to cruel and violent cues in men by promoting extended viewing of violent stimuli.[90] Testosterone specific structural brain characteristic can predict aggressive behaviour in individuals.[91]
Estradiol is known to correlate with aggression in male mice.[92] Moreover, the conversion of testosterone to estradiol regulates male aggression in sparrows during breeding season.[93] Rats who were given anabolic steroids that increase testosterone were also more physically aggressive to provocation as a result of "threat sensitivity".[94]
Brain[edit]
The brain is also affected by this sexual differentiation;[13] the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with congenital diseases of androgen formation or androgen receptor function, to be associated with functional androgen receptors.[95]
There are some differences between a male and female brain (possibly the result of different testosterone levels), one of them being size: the male human brain is, on average, larger.[96] Men were found to have a total myelinated fiber length of 176 000 km at the age of 20, whereas in women the total length was 149 000 km (approx. 15% less).[97]
No immediate short term effects on mood or behavior were found from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men.[98] A correlation between testosterone and risk tolerance in career choice exists among women.[64][99]
Attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer's type,[100][101][102][103] a key argument in life extension medicine for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone,[104] where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.
Medical use[edit]
Main article: Testosterone (medication)
Testosterone is used as a medication for the treatment of males with too little or no natural testosterone production, certain forms of breast cancer,[10] and gender dysphoria in transgender men. This is known as hormone replacement therapy (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range. Decline of testosterone production with age has led to interest in androgen replacement therapy.[105] It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.[106]
Testosterone is included in the World Health Organization's list of essential medicines, which are the most important medications needed in a basic health system.[107] It is available as a generic medication.[10] The price depends on the form of testosterone used.[108] It can be administered as a cream or transdermal patch that is applied to the skin, by injection into a muscle, as a tablet that is placed in the cheek, or by ingestion.[10]
Common side effects from testosterone medication include acne, swelling, and breast enlargement in males.[10] Serious side effects may include liver toxicity, heart disease, and behavioral changes.[10] Women and children who are exposed may develop virilization.[10] It is recommended that individuals with prostate cancer not use the medication.[10] It can cause harm if used during pregnancy or breastfeeding.[10]
Biological activity[edit]
Steroid hormone activity[edit]
The effects of testosterone in humans and other vertebrates occur by way of multiple mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors.[109][110] Androgens such as testosterone have also been found to bind to and activate membrane androgen receptors.[111][112][113]
Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T.[114] The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.
Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of biological differences between males and females.
The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of aromatization to estradiol. In the bones, estradiol accelerates ossification of cartilage into bone, leading to closure of the epiphyses and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting LH secretion).[115] In many mammals, prenatal or perinatal "masculinization" of the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.[116]
Neurosteroid activity[edit]
Testosterone, via its active metabolite 3α-androstanediol, is a potent positive allosteric modulator of the GABAA receptor.[117]
Testosterone has been found to act as an antagonist of the TrkA and p75NTR, receptors for the neurotrophin nerve growth factor (NGF), with high affinity (around 5 nM).[118][119][120] In contrast to testosterone, DHEA and DHEA sulfate have been found to act as high-affinity agonists of these receptors.[118][119][120]
Testosterone is an antagonist of the sigma σ1 receptor (Ki = 1,014 or 201 nM).[121] However, the concentrations of testosterone required for binding the receptor are far above even total circulating concentrations of testosterone in adult males (which range between 10 and 35 nM).[122]
Biochemistry[edit]
Human steroidogenesis, showing testosterone near bottom.[123]
Biosynthesis[edit]
Like other steroid hormones, testosterone is derived from cholesterol (see figure).[124] The first step in the biosynthesis involves the oxidative cleavage of the side-chain of cholesterol by cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), a mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. In the next step, two additional carbon atoms are removed by the CYP17A1 (17α-hydroxylase/17,20-lyase) enzyme in the endoplasmic reticulum to yield a variety of C19 steroids.[125] In addition, the 3β-hydroxyl group is oxidized by 3β-hydroxysteroid dehydrogenase to produce androstenedione. In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield testosterone.
The largest amounts of testosterone (>95%) are produced by the testes in men,[2] while the adrenal glands account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, thecal cells of the ovaries, and, during pregnancy, by the placenta.[126] In the testes, testosterone is produced by the Leydig cells.[127] The male generative glands also contain Sertoli cells, which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone-binding globulin (SHBG).
Regulation[edit]
Hypothalamic–pituitary–testicular axis
In males, testosterone is synthesized primarily in Leydig cells. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17β-hydroxysteroid dehydrogenase.[128]
The amount of testosterone synthesized is regulated by the hypothalamic–pituitary–testicular axis (see figure to the right).[129] When testosterone levels are low, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus, which in turn stimulates the pituitary gland to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.
Factors affecting testosterone levels may include:
Age: Testosterone levels gradually reduce as men age.[130][131] This effect is sometimes referred to as andropause or late-onset hypogonadism.[132]
Exercise: Resistance training increases testosterone levels,[133] however, in older men, that increase can be avoided by protein ingestion.[134] Endurance training in men may lead to lower testosterone levels.[135]
Nutrients: Vitamin A deficiency may lead to sub-optimal plasma testosterone levels.[136] The secosteroid vitamin D in levels of 400–1000 IU/d (10–25 µg/d) raises testosterone levels.[137] Zinc deficiency lowers testosterone levels[138] but over-supplementation has no effect on serum testosterone.[139]
Weight loss: Reduction in weight may result in an increase in testosterone levels. Fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone.[140] However no clear association between body mass index and testosterone levels has been found.[141]
Miscellaneous: Sleep: (REM sleep) increases nocturnal testosterone levels.[142] Behavior: Dominance challenges can, in some cases, stimulate increased testosterone release in men.[143] Drugs: Natural or man-made antiandrogens including spearmint tea reduce testosterone levels.[144][145][146] Licorice can decrease the production of testosterone and this effect is greater in females.[147]
Distribution[edit]
The plasma protein binding of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound.[148] It is bound 65% to sex hormone-binding globulin (SHBG) and 33% bound weakly to albumin.[149]
Plasma protein binding of testosterone and dihydrotestosterone show
Metabolism[edit]
vte Testosterone metabolism in humans
Testosterone structures
The image above contains clickable linksTestosterone metabolism in humans. Conjugation (sulfation and glucuronidation) occurs both with testosterone and with all of the other steroids that have one or more available hydroxyl (-OH) groups in this diagram.
Both testosterone and 5α-DHT are metabolized mainly in the liver.[1][151] Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively.[1] An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order.[1][151][152] Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone.[1][151] The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile.[1][151][152] Only a small fraction (2%) of testosterone is excreted unchanged in the urine.[151]
In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively.[1][151] Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively.[1][151] Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion.[1][151] 3β-Androstanediol and 3β-etiocholanediol can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into epiandrosterone and epietiocholanolone, respectively.[153][154] A small portion of approximately 3% of testosterone is reversibly converted in the liver into androstenedione by 17β-HSD.[152]
In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6.[155] 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.[155] The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism.[155] In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites.[155][156] Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.[155]
Two of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues.[151] Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by aromatase.[2][151][157][158] 5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides),[159] skin, hair follicles, and brain[160] and aromatase is highly expressed in adipose tissue, bone, and the brain.[161][162] As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression,[152] and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone,[163] it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.[164]
Levels[edit]
Total levels of testosterone in the body are 264 to 916 ng/dL in men age 19 to 39 years,[165] while mean testosterone levels in adult men have been reported as 630 ng/dL.[166] Levels of testosterone in men decline with age.[165] In women, mean levels of total testosterone have been reported to be 32.6 ng/dL.[167][168] In women with hyperandrogenism, mean levels of total testosterone have been reported to be 62.1 ng/dL.[167][168]
Testosterone levels in males and females show
Total testosterone levels in males throughout life show
Reference ranges for blood tests, showing adult male testosterone levels in light blue at center-left.
Measurement[edit]
Testosterone’s bioavailable concentration is commonly determined using the Vermeulen calculation or more precisely using the modified Vermeulen method,[174][175] which considers the dimeric form of sex-hormone-binding-globulin.[176]
Both methods use chemical equilibrium to derive the concentration of bioavailable testosterone: in circulation testosterone has two major binding partners, albumin (weakly bound) and sex-hormone-binding-globulin (strongly bound). These methods are described in detail in the accompanying figure.
Dimeric sex-hormone-binding-globulin with its testosterone ligands
Two methods for determining concentration of bioavailable testosterone.
History[edit]
A testicular action was linked to circulating blood fractions – now understood to be a family of androgenic hormones – in the early work on castration and testicular transplantation in fowl by Arnold Adolph Berthold (1803–1861).[177] Research on the action of testosterone received a brief boost in 1889, when the Harvard professor Charles-Édouard Brown-Séquard (1817–1894), then in Paris, self-injected subcutaneously a "rejuvenating elixir" consisting of an extract of dog and guinea pig testicle. He reported in The Lancet that his vigor and feeling of well-being were markedly restored but the effects were transient,[178] and Brown-Séquard's hopes for the compound were dashed. Suffering the ridicule of his colleagues, he abandoned his work on the mechanisms and effects of androgens in human beings.
In 1927, the University of Chicago's Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles — the Chicago stockyards — and recruited students willing to endure the tedious work of extracting their isolates. In that year, Koch and his student, Lemuel McGee, derived 20 mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, remasculinized them.[179] The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—Schering (Berlin, Germany), Organon (Oss, Netherlands) and Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930s.
Nobel Prize winner, Leopold Ruzicka of Ciba, a pharmaceutical industry giant that synthesized testosterone.
The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)".[180] They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The structure was worked out by Schering's Adolf Butenandt, at the Chemisches Institut of Technical University in Gdańsk.[181][182]
The chemical synthesis of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch.[183] Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, published their synthesis of testosterone.[184] These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry.[182][185] Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C19H28O2), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.
The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group[186] was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",[187] and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and well-being.[188]
Other animals[edit]
Testosterone is observed in most vertebrates. Testosterone and the classical nuclear androgen receptor first appeared in gnathostomes (jawed vertebrates).[189] Agnathans (jawless vertebrates) such as lampreys do not produce testosterone but instead use androstenedione as a male sex hormone.[190] Fish make a slightly different form called 11-ketotestosterone.[191] Its counterpart in insects is ecdysone.[192] The presence of these ubiquitous steroids in a wide range of animals suggest that sex hormones have an ancient evolutionary history.[193]
Sprouts are rich in digestible energy, bioavailable vitamins, minerals, amino acids, proteins, beneficial enzymes and phytochemicals, as these are necessary for a germinating plant to grow . These nutrients are essential for human health. To clarify, the nutritional changes upon germination & sprouting have been summarized below. Chavan and Kadam (1989) concluded that - “The desirable nutritional changes that occur during sprouting are mainly due to the breakdown of complex compounds into a more simple form, transformation into essential constituents and breakdown of nutritionally undesirable constituents.”
“The metabolic activity of resting seeds increases as soon as they are hydrated during soaking. Complex biochemical changes occur during hydration and subsequent sprouting. The reserve chemical constituents, such as protein, starch and lipids, are broken down by enzymes into simple compounds that are used to make new compounds.”
“Sprouting grains causes increased activities of hydrolytic enzymes, improvements in the contents of total proteins, fat, certain essential amino acids, total sugars, B-group vitamins, and a decrease in dry matter, starch and anti-nutrients. The increased contents of protein, fat, fibre and total ash are only apparent and attributable to the disappearance of starch. However, improvements in amino acid composition, B-group vitamins, sugars, protein and starch digestibilities, and decrease in phytates and protease inhibitors are the metabolic effects of the sprouting process.”
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn. Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States, Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70% to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn. Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel. When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
ORNAMENTAL AND OTHER USES
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn. Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States, Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70% to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn. Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel. When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
ORNAMENTAL AND OTHER USES
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn. Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States, Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70% to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn. Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel. When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
ORNAMENTAL AND OTHER USES
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Humans and their hominid ancestors have consumed eggs for millions of years. The most widely consumed eggs are those of fowl, especially chickens. People in Southeast Asia began harvesting chicken eggs for food by 1500 BCE. Eggs of other birds, such as ducks and ostriches, are eaten regularly but much less commonly than those of chickens. People may also eat the eggs of reptiles, amphibians, and fish. Fish eggs consumed as food are known as roe or caviar.
Chickens and other egg-laying creatures are raised throughout the world, and mass production of chicken eggs is a global industry. In 2009, an estimated 62.1 million metric tons of eggs were produced worldwide from a total laying flock of approximately 6.4 billion hens. There are issues of regional variation in demand and expectation, as well as current debates concerning methods of mass production. In 2012, the European Union banned battery husbandry of chickens.
History
Bird eggs have been valuable foodstuffs since prehistory, in both hunting societies and more recent cultures where birds were domesticated. The chicken was most likely domesticated for its eggs (from jungle fowl native to tropical and subtropical Southeast Asia and Indian subcontinent) before 7500 BCE. Chickens were brought to Sumer and Egypt by 1500 BCE, and arrived in Greece around 800 BCE, where the quail had been the primary source of eggs. In Thebes, Egypt, the tomb of Haremhab, dating to approximately 1420 BCE, shows a depiction of a man carrying bowls of ostrich eggs and other large eggs, presumably those of the pelican, as offerings. In ancient Rome, eggs were preserved using a number of methods and meals often started with an egg course. The Romans crushed the shells in their plates to prevent evil spirits from hiding there.
In the Middle Ages, eggs were forbidden during Lent because of their richness, although the motivation for forgoing eggs during Lent was not entirely religious. An annual pause in egg consumption allowed farmers to rest their flocks, and also to limit their hens' consumption of feed during a time of year when food stocks were usually scarce.
Eggs scrambled with acidic fruit juices were popular in France in the seventeenth century; this may have been the origin of lemon curd.
The dried egg industry developed in the nineteenth century, before the rise of the frozen egg industry. In 1878, a company in St. Louis, Missouri started to transform egg yolk and egg white into a light-brown, meal-like substance by using a drying process. The production of dried eggs significantly expanded during World War II, for use by the United States Armed Forces and its allies.
In 1911, the egg carton was invented by Joseph Coyle in Smithers, British Columbia, to solve a dispute about broken eggs between a farmer in Bulkley Valley and the owner of the Aldermere Hotel. Early egg cartons were made of paper.[9] Polystyrene egg cartons became popular in the latter half of the twentieth century as they were perceived to offer better protection especially against heat and breakage, however, by the twenty-first century environmental considerations have led to the return of more biodegradable paper cartons (often made of recycled material) that once again became more widely used.
Whereas the wild Asian fowl from which domesticated chickens are descended typically lay about a dozen eggs each year during the breeding season, several millennia of selective breeding have produced domesticated hens capable of laying more than three hundred eggs each annually, and to lay eggs year round.
Varieties
Bird eggs are a common food and one of the most versatile ingredients used in cooking. They are important in many branches of the modern food industry.
The most commonly used bird eggs are those from the chicken, duck, and goose. Smaller eggs, such as quail eggs, are used occasionally as a gourmet ingredient in Western countries. Eggs are a common everyday food in many parts of Asia, such as China and Thailand, with Asian production providing 59 percent of the world total in 2013.
The largest bird eggs, from ostriches, tend to be used only as special luxury food. Gull eggs are considered a delicacy in England, as well as in some Scandinavian countries, particularly in Norway. In some African countries, guineafowl eggs often are seen in marketplaces, especially in the spring of each year. Pheasant eggs and emu eggs are edible, but less widely available; sometimes they are obtainable from farmers, poulterers, or luxury grocery stores. In many countries, wild bird eggs are protected by laws which prohibit the collecting or selling of them, or permit collection only during specific periods of the year.
Culinary properties
Chicken eggs are widely used in many types of dishes, both sweet and savory, including many baked goods. Some of the most common preparation methods include scrambled, fried, poached, hard-boiled, soft-boiled, omelettes, and pickled. They also may be eaten raw, although this is not recommended for people who may be especially susceptible to salmonellosis, such as the elderly, the infirm, or pregnant women. In addition, the protein in raw eggs is only 51 percent bioavailable, whereas that of a cooked egg is nearer 91 percent bioavailable, meaning the protein of cooked eggs is nearly twice as absorbable as the protein from raw eggs.
As a cooking ingredient, egg yolks are an important emulsifier in the kitchen, and are also used as a thickener, as in custards.
The albumen (egg white) contains protein, but little or no fat, and may be used in cooking separately from the yolk. The proteins in egg white allow it to form foams and aerated dishes. Egg whites may be aerated or whipped to a light, fluffy consistency, and often are used in desserts such as meringues and mousse.
Ground eggshells sometimes are used as a food additive to deliver calcium. Every part of an egg is edible, although the eggshell is generally discarded. Some recipes call for immature or unlaid eggs, which are harvested after the hen is slaughtered or cooked, while still inside the chicken.
Cooking
Eggs contain multiple proteins that gel at different temperatures within the yolk and the white, and the temperature determines the gelling time. Egg yolk becomes a gel, or solidifies, between 61 and 70 °C (142 and 158 °F). Egg white gels at different temperatures: 60 to 73 °C (140 to 163 °F). The white contains exterior albumen which sets at the highest temperature. In practice, in many cooking processes the white gels first because it is exposed to higher temperatures for longer.
Salmonella is killed instantly at 71 °C (160 °F), but also is killed from 54.5 °C (130.1 °F), if held at that temperature for sufficiently long time periods. To avoid the issue of salmonella, eggs may be pasteurized in-shell at 57 °C (135 °F) for an hour and 15 minutes. Although the white then is slightly milkier, the eggs may be used in normal ways. Whipping for meringue takes significantly longer, but the final volume is virtually the same.
If a boiled egg is overcooked, a greenish ring sometimes appears around the egg yolk due to changes to the iron and sulfur compounds in the egg. It also may occur with an abundance of iron in the cooking water. Overcooking harms the quality of the protein. Chilling an overcooked egg for a few minutes in cold water until it is completely cooled may prevent the greenish ring from forming on the surface of the yolk.
Peeling a cooked egg is easiest when the egg was put into boiling water as opposed to slowly heating the egg from a start in cold water.
Flavor variations
Although the age of the egg and the conditions of its storage have a greater influence, the bird's diet affects the flavor of the egg. For example, when a brown-egg chicken breed eats rapeseed (canola) or soy meals, its intestinal microbes metabolize them into fishy-smelling triethylamine, which ends up in the egg. The unpredictable diet of free-range hens will produce likewise, unpredictable egg flavors.[7] Duck eggs tend to have a flavor distinct from, but still resembling, chicken eggs.
Eggs may be soaked in mixtures to absorb flavor. Tea eggs, a common snack sold from street-side carts in China, are steeped in a brew from a mixture of various spices, soy sauce, and black tea leaves to give flavor.
Storage
Careful storage of edible eggs is extremely important, as an improperly handled egg may contain elevated levels of Salmonella bacteria that may cause severe food poisoning. In the US, eggs are washed. This cleans the shell, but erodes its cuticle. The USDA thus recommends refrigerating eggs to prevent the growth of Salmonella.
Refrigeration also preserves the taste and texture, however, intact eggs (unwashed and unbroken) may be left unrefrigerated for several months without spoiling. In Europe, eggs are not usually washed, and the shells are dirtier, however the cuticle is undamaged, and they do not require refrigeration. In the UK in particular, hens are immunized against salmonella and generally, their eggs are safe for 21 days.
Preservation
The simplest method to preserve an egg is to treat it with salt. Salt draws water out of bacteria and molds, which prevents their growth. The Chinese salted duck egg is made by immersing duck eggs in brine, or coating them individually with a paste of salt and mud or clay. The eggs stop absorbing salt after approximately a month, having reached osmotic equilibrium. Their yolks take on an orange-red color and solidify, but the white remains somewhat liquid. These often are boiled before consumption and are served with rice congee.
Another method is to make pickled eggs, by boiling them first and immersing them in a mixture of vinegar, salt, and spices, such as ginger or allspice. Frequently, beetroot juice is added to impart a red color to the eggs. If the eggs are immersed in it for a few hours, the distinct red, white, and yellow colors may be seen when the eggs are sliced. If marinated for several days or more, the red color will reach the yolk. If the eggs are marinated in the mixture for several weeks or more, the vinegar will dissolve much of the shell's calcium carbonate and penetrate the egg, making it acidic enough to inhibit the growth of bacteria and molds. Pickled eggs made this way generally keep for a year or more without refrigeration.
A century egg or hundred-year-old egg is preserved by coating an egg in a mixture of clay, wood ash, salt, lime, and rice straw for several weeks to several months, depending on the method of processing. After the process is completed, the yolk becomes a dark green, cream-like substance with a strong odor of sulfur and ammonia, while the white becomes a dark brown, transparent jelly with a comparatively mild, distinct flavor. The transforming agent in a century egg is its alkaline material, which gradually raises the pH of the egg from approximately 9 to 12 or more. This chemical process breaks down some of the complex, flavorless proteins and fats of the yolk into simpler, flavorful ones, which in some way may be thought of as an "inorganic" version of fermentation.
Nutrition and health effects
Chicken egg
whole, hard-boiled
Nutritional value per 100 g (3.5 oz)
Energy647 kJ (155 kcal)
Carbohydrates
1.12 g
Fat
10.6 g
Protein
12.6 g
Tryptophan0.153 g
Threonine0.604 g
Isoleucine0.686 g
Leucine1.075 g
Lysine0.904 g
Methionine0.392 g
Cystine0.292 g
Phenylalanine0.668 g
Tyrosine0.513 g
Valine0.767 g
Arginine0.755 g
Histidine0.298 g
Alanine0.700 g
Aspartic acid1.264 g
Glutamic acid1.644 g
Glycine0.423 g
Proline0.501 g
Serine0.936 g
VitaminsQuantity%DV†
Vitamin A equiv.19%149 μg
Thiamine (B1)6%0.066 mg
Riboflavin (B2)42%0.5 mg
Niacin (B3)0%0.064 mg
Pantothenic acid (B5)28%1.4 mg
Vitamin B69%0.121 mg
Folate (B9)11%44 μg
Vitamin B1246%1.11 μg
Choline60%294 mg
Vitamin D15%87 IU
Vitamin E7%1.03 mg
Vitamin K0%0.3 μg
MineralsQuantity%DV†
Calcium5%50 mg
Iron9%1.2 mg
Magnesium3%10 mg
Phosphorus25%172 mg
Potassium4%126 mg
Sodium8%126 mg
Zinc11%1.0 mg
Other constituentsQuantity
Water75 g
Cholesterol373 mg
For edible portion only.
Refuse: 12% (shell).
An egg just large enough to be classified as "large" in the U.S. yields 50 grams of egg without shell. This size egg is classified as "medium" in Europe and "standard" in New Zealand.
Link to USDA Database entry
Units
μg = micrograms • mg = milligrams
IU = International units
†Percentages are roughly approximated using US recommendations for adults.
Source: USDA FoodData Central
Egg yolks and whole eggs store significant amounts of protein and choline. Due to their protein content, the United States Department of Agriculture formerly categorized eggs as Meat within the Food Guide Pyramid (now MyPlate).
A 50-gram (1.8 oz) medium/large chicken egg provides approximately 70 kilocalories (290 kJ) of food energy and 6 grams of protein.
Eggs (boiled) supply several vitamins and minerals as significant amounts of the Daily Value (DV), including (per 100g) vitamin A (19% DV), riboflavin (42% DV), pantothenic acid (28% DV), vitamin B12 (46% DV), choline (60% DV), phosphorus (25% DV), zinc (11% DV) and vitamin D (15% DV). Cooking methods affect the nutritional values of eggs.[clarify]
The diet of laying hens also may affect the nutritional quality of eggs. For instance, chicken eggs that are especially high in omega-3 fatty acids are produced by feeding hens a diet containing polyunsaturated fats from sources such as fish oil, chia seeds, or flaxseeds. Pasture-raised free-range hens, which forage for their own food, also produce eggs that are relatively enriched in omega-3 fatty acids when compared to those of cage-raised chickens.
A 2010 USDA study determined there were no significant differences of macronutrients in various chicken eggs.[53]
Cooked eggs are easier to digest than raw eggs,[54] as well as having a lower risk of salmonellosis.
Cholesterol and fat
More than half the calories found in eggs come from the fat in the yolk; 50 grams of chicken egg (the contents of an egg just large enough to be classified as "large" in the US, but "medium" in Europe) contains approximately five grams of fat. Saturated fat (palmitic, stearic, and myristic acids) makes up 27 percent of the fat in an egg. The egg white consists primarily of water (88 percent) and protein (11 percent), with no cholesterol and 0.2 percent fat.
There is debate over whether egg yolk presents a health risk. Some research suggests dietary cholesterol increases the ratio of total to HDL cholesterol and, therefore, adversely affects the body's cholesterol profile; whereas other studies show that moderate consumption of eggs, up to one a day, does not appear to increase heart disease risk in healthy individuals. Harold McGee argues that the cholesterol in the egg yolk is not what causes a problem, because fat (particularly saturated fat) is much more likely to raise cholesterol levels than the consumption of cholesterol.
A popular Easter tradition in some parts of the world is a decoration of hard-boiled eggs (usually by dyeing, but often by spray-painting). A similar tradition of egg painting exists in areas of the world influenced by the culture of Persia. Before the spring equinox in the Persian New Year tradition (called Norouz), each family member decorates a hard-boiled egg and they set them together in a bowl.
In the New Testament, eggs are referred to as an example of the kind of gift a child might request from their father, and which would not be denied.
In Northern Europe and North America, Easter eggs may be hidden by adults for children to find in an Easter egg hunt. They may be rolled in some traditions.
In Eastern and Central Europe, and parts of England, easter eggs may be tapped against each other to see whose egg breaks first.
Since the sixteenth century, the tradition of a dancing egg is held during the feast of Corpus Christi in Barcelona and other Catalan cities. It consists of a hollow eggshell, positioned over the water jet from a fountain, which causes the eggshell to revolve without falling.
Feel free to use this image, just link to www.enzymlogic.com.
MET over-expression, aberrant autocrine or paracrine ligand production, and missense MET mutations are mechanisms that lead to activation of the MET pathway in tumors and are associated with poor prognostic outcome. Scientists have developed a potent, orally bioavailable, inhibitor LY2801653 targeting MET kinase with promising anti-tumor activities in mouse xenograft models.
LY2801653 is a slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM and a pharmacodynamic residence time of 8.5 hours. The crystal structure of MET bound with LY2801653 indicates that LY2801653 is a type II ATP competitive inhibitor and illustrates that the mechanism of inhibition is through the stabilization of the inactive conformation. LY2801653 has also demonstrated in vitro effects on MET pathway-dependent cell scattering and cell proliferation, in vivo antitumor effects in MET amplified, MET autocrine and MET over-expressed xenograft models; and in vivo vessel normalization effects.
Furthermore, the binding of LY2801653 to MET appears to contribute 2 clinically intriguing features: the potential ability to retain potency versus a spectrum of mutations and the ability to sustain target inhibition due to its slow off-rate.
In the present study LY2801653 has been found to have potent activity against several other oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2 and MKNK1/2. In view of the reported transforming activity of these kinases, there may be clinical merit in evaluating LY2801653. In human bladder cancer, overexpression of MET/AXL/PDGFRA was shown to correlate with poor survival and contributed to the progression of human bladder cancer. ROS1 fusion proteins are found in glioblastoma, NSCLC and cholangiocarcinoma. MKNK1/2 are capable of regulating translation through the direct phosphorylation of eIF4E. Increased MKNK1/2-dependent phosphorylation of eIF4E is observed in head and neck squamous cell carcinoma and is correlated with a poor prognosis. Overexpression and activating mutations of DDR1/2 has been reported in sarcoma and in squamous cell lung cancer respectively.
All these observations have supported the progression of LY2801653 into clinical testing in an ongoing phase 1 study.
Winter warmth 🍲 Just when the tulips began to push the tips of their leaves up, we awakened to another 30cm of snow, it seems winter isn’t ready to let go quite yet, and so another pot of warming soup is on the stove. Doukhobor Borscht is a decadent, creamy affair of sweet braised cabbage, an abundance of shredded vegetables, a delicate vegetable broth, satisfying texture- the complete opposite of traditional Polish Barszcz I grew up on, the latter a clear, deep purple broth on a base of fermented beet Kvass. Both my girls always have seconds when this is on the table, dipping thick wedges of crusty homemade buttered sourdough into their bowls. Every meal is an opportunity for conscious nutrition, for feeding the microbiome, for incorporating essential minerals and anti inflammatory foods. Some staple additions to soups for us are 1) Some kind of wild foraged seaweed for minerals, cancer fighting compounds, and a myriad of other benefits. This is usually Kelp, today it was Sea grapes (from Feather Boa Kelp) and some purple Nori. 2) Crushed garlic left to rest for 10 minutes post crushing to activate the allicin compounds (if it is chopped & heated without rest, the potent health benefits are lost) 3) Turmeric grated fresh with fresh ground pepper (piperine enhances curcumin absorption in the body by up to 2000%, combining the spices magnifies the health benefits & makes them bioavailable for absorption) 4) adding every allium I have on hand (in this case there are onions, leeks, garlic and scallion) 5) Making all soups on a foundation of nourishing homemade bone broth, which I keep on hand in the freezer and use in lieu of water when cooking grains like rice as well. 6) Medicinal wild mushrooms that I have harvested & dried are also frequently added, a chunk of Chaga with bone broth, powdered Chicken of the Woods or Turkey Tail, all are easily incorporated into daily meals. These simple but conscious changes don’t contribute much to flavour (the taste doesn’t really change) but these seemingly simple swaps tremendously increase the nutritional value of each meal. #consciousnutrition #slowfood #wildharvest #eatyourmedicine #nourishingtraditions #nourish #earth
Um texto, em português, da Wikipédia:
Hibiscus
Hibiscus L. é um gênero botânico, com cerca de 300 espécies, inserido na família das Malvaceae, com flores e folhas exuberantes. Devido à nova taxonomia pela filogenética (Angiosperm Phylogeny Group), muitas espécies que pertenciam a esse gênero estão migrando para outros gêneros. Por exemplo: Hibiscus esculentus L., a planta do quiabo, agora é Abelmoschus esculentus (L.) Moench. O cultivo dos exemplares do gênero, tanto ornamental como econômico, está disseminado nas regiões subtropicais e tropicais, cuidando para não sofrerem com geadas e temperaturas baixas constantes.
Etimologia:
Hibiscus significa Ísis (deusa egípcia), em grego.
Sinonímia:
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W. Fitzg.
Fioria Mattei
Espécies:
Hibiscus acetosella
Hibiscus x archeri (híbrido)
Hibiscus arnottianus
Hibiscus bifurcatus
Hibiscus brackenridgei
Hibiscus calyphyllus
Hibiscus cameronii
Hibiscus cannabinus
Hibiscus chitra
Hibiscus cisplatinus
Hibiscus clayi
Hibiscus coccineus
Hibiscus denisonii
Hibiscus diversifolius
Hibiscus elatus
Hibiscus furcellatus
Hibiscus fuscus
Hibiscus grandiflorus
Hibiscus hastatus
Hibiscus heterophyllus
Hibiscus indicus
Hibiscus kokio
Hibiscus lasiocarpos
Hibiscus lavaterioides
Hibiscus lobatus
Hibiscus ludwigii
Hibiscus macrophyllus
Hibiscus mastersianus
Hibiscus militaris
Hibiscus moscheutos
Hibiscus mutabilis (malva-rosa)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis (guanxuma-do-mangue)
Hibiscus platanifolius
Hibiscus radiatus
Hibiscus rosa-sinensis (hibisco)
Hibiscus sabdariffa (vinagreira)
Hibiscus schizopetalus (hibisco-crespo)
Hibiscus scottii
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus syriacus (hibisco-da-síria)
Hibiscus tiliaceus (algodoeiro-da-praia)
Hibiscus trionum (flor-de-todas-as-horas)
Hibiscus waimeae
Hibiscus dioscorides
Hibiscus diriffan
Hibiscus escobariae
Hibiscus noli-tangere
Hibiscus quattenensis
Hibiscus socotranus
Hibiscus stenanthus
Portugal:
Em Portugal este género está representado por 2 espécies, presentes em Portugal Continental, a primeira nativa, a segunda introduzida:1
Hibiscus palustris L.
Hibiscus trionum L.
Classificação do gênero:
Sistema Classificação Referência
Linné Classe Monadelphia, ordem Polyandria Species plantarum (1753)
Papuodendron C. T. White
Pariti Adans.
Talipariti Fryxell
Wilhelminia Hochr.
A text, in english, from Wikipedia, the free encyclopedia:
Hibiscus
For other uses, see Hibiscus (disambiguation).
Hibiscus
Hibiscus flower TZ.jpg
Hibiscus rosa-sinensis
Scientific classification
Kingdom: Plantae
Division: Angiosperms
Class: Eudicots
Order: Malvales
Family: Malvaceae
Subfamily: Malvoideae
Tribe: Hibisceae
Genus: Hibiscus
L.
Species
232 species
Synonyms
Bombycidendron Zoll. & Moritzi
Bombycodendron Hassk.
Brockmania W.Fitzg.
Pariti Adans.
Wilhelminia Hochr.
Hibiscus (/hɨˈbɪskəs/ or /haɪˈbɪskəs/) is a genus of flowering plants in the mallow family, Malvaceae. It is quite large, containing several hundred species that are native to warm-temperate, subtropical and tropical regions throughout the world. Member species are often noted for their showy flowers and are commonly known simply as hibiscus, or less widely known as rose mallow. The genus includes both annual and perennial herbaceous plants, as well as woody shrubs and small trees. The generic name is derived from the Greek word ἱβίσκος (hibískos), which was the name Pedanius Dioscorides (ca. 40–90) gave to Althaea officinalis.
Description:
The leaves are alternate, ovate to lanceolate, often with a toothed or lobed margin. The flowers are large, conspicuous, trumpet-shaped, with five or more petals, color from white to pink, red, orange, purple or yellow, and from 4–18 cm broad. Flower color in certain species, such as H. mutabilis and H. tiliaceus, changes with age.[5] The fruit is a dry five-lobed capsule, containing several seeds in each lobe, which are released when the capsule dehisces (splits open) at maturity. It is of red and white colours. It is an example of complete flowers.
Uses:
Symbolism and culture
Hibiscus species represent nations: Hibiscus syriacus is the national flower of South Korea, and Hibiscus rosa-sinensis is the national flower of Malaysia. The hibiscus is the national flower of Haiti. The red hibiscus is the flower of the Hindu goddess Kali, and appears frequently in depictions of her in the art of Bengal, India, often with the goddess and the flower merging in form. The hibiscus is used as an offering to goddess Kali and Lord Ganesha in Hindu worship.
In the Philippines, the gumamela (local name for hibiscus) is used by children as part of a bubble-making pastime. The flowers and leaves are crushed until the sticky juices come out. Hollow papaya stalks are then dipped into this and used as straws for blowing bubbles.
The hibiscus flower is traditionally worn by Tahitian and Hawaiian girls. If the flower is worn behind the left ear, the woman is married or in a relationship. If the flower is worn on the right, she is single or openly available for a relationship. The hibiscus is Hawaii's state flower.
Nigerian author Chimamanda Ngozi Adichie named her first novel Purple Hibiscus after the delicate flower.
The bark of the hibiscus contains strong bast fibres that can be obtained by letting the stripped bark set in the sea to let the organic material rot away.
Landscaping
Many species are grown for their showy flowers or used as landscape shrubs, and are used to attract butterflies, bees, and hummingbirds.
Paper
One species of Hibiscus, known as kenaf (Hibiscus cannabinus), is extensively used in paper-making.
Beverage
Main article: Hibiscus tea
The tea made of hibiscus flowers is known by many names in many countries around the world and is served both hot and cold. The beverage is well known for its color, tanginess and flavor.
It is known as bissap in West Africa, agua de jamaica in Mexico and Honduras (the flower being flor de jamaica) and gudhal (गुड़हल) in India. Some refer to it as roselle, a common name for the hibiscus flower. In Jamaica, Trinidad and many other islands in the Caribbean, the drink is known as sorrel (Hibiscus sabdariffa; not to be confused with Rumex acetosa, a species sharing the common name sorrel). In Ghana, the drink is known as soobolo in one of the local languages.
Roselle is typically boiled in an enamel-coated large stock pot as most West Indians believe the metal from aluminum, steel or copper pots will destroy the natural minerals and vitamins.[citation needed]
In Cambodia, a cold beverage can be prepared by first steeping the petals in hot water until the colors are leached from the petals, then adding lime juice (which turns the beverage from dark brown/red to a bright red), sweeteners (sugar/honey) and finally cold water/ice cubes.
In Egypt,[citation needed] Sudan and the Arab world, hibiscus tea is known as karkadé (كركديه), and is served as both a hot and a cold drink.
Food
Dried hibiscus is edible, and it is often a delicacy in Mexico. It can also be candied and used as a garnish.
The roselle (Hibiscus sabdariffa) is used as a vegetable. The species Hibiscus suratensis Linn synonymous to Hibiscus aculeatus G. Don is noted in Visayas Philippines being a souring ingredient for almost all local vegetables and menus. Known as Labog in the Visayan area, (or Labuag/Sapinit in Tagalog), the species is a very good ingredient in cooking native chicken soup. Certain species of hibiscus are also beginning to be used more widely as a natural source of food coloring (E163),[citation needed] and replacement of Red #3 / E127.
Hibiscus species are used as food plants by the larvae of some Lepidopteran species, including Chionodes hibiscella, Hypercompe hambletoni, the nutmeg moth, and the turnip moth.
Health benefits
The tea is popular as a natural diuretic; it contains vitamin C and minerals, and is used traditionally as a mild medicine.
A 2008 USDA study shows consuming hibiscus tea lowers blood pressure in a group of prehypertensive and mildly hypertensive adults. Three cups of tea daily resulted in an average drop of 8.1 mmHg in their systolic blood pressure, compared to a 1.3 mmHg drop in the volunteers who drank the placebo beverage. Study participants with higher blood pressure readings (129 or above) had a greater response to hibiscus tea: their systolic blood pressure went down by 13.2 mmHg. These data support the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required.
Studies have demonstrated the anti-hypertensive effects of H. sabdariffa in both humans and animals. It has been proposed that the antihypertensive effects of H. sabdariffa is due to its angiotensin-converting enzyme inhibiting activity. In a randomized, controlled clinical trial involving 39 patients with mild to moderate hypertension, Captopril was compared to an extract of H. sabdariffa for antihypertensive effects. Subjects taking an extract of H.sabdariffa, consumed daily before breakfast for four weeks, found reduction in blood pressure similar to Captopril. Another randomized, placebo clinical trial involving 54 study participants with moderate hypertension demonstrated a reduction in both systolic and diastolic blood pressure. However upon discontinuation of treatment, both systolic and diastolic blood pressures were subsequently elevated.
Hibiscus rosa-sinensis has a number of medical uses in Chinese herbology. Lokapure s.g.et al. their research indicates some potential in cosmetic skin care; for example, an extract from the flowers of Hibiscus rosa- sinensis has been shown to function as an anti-solar agent by absorbing ultraviolet radiation.
In the Indian traditional system of medicine, Ayurveda, hibiscus, especially white hibiscus and red hibiscus (Hibiscus rosa-sinensis), is considered to have medicinal properties. The roots are used to make various concoctions believed to cure ailments such as cough, hair loss or hair greying. As a hair treatment, the flowers are boiled in oil along with other spices to make a medicated hair oil. The leaves and flowers are ground into a fine paste with a little water, and the resulting lathery paste is used as a shampoo plus conditioner.
Hibiscus tea also contains bioflavonoids, which are believed to help prevent an increase in LDL cholesterol, which can increase the buildup of plaque in the arteries.
A previous animal study demonstrated the effects of H.sabdariffa extract on atherosclerosis in rabbits. Notably, a reduction in triglyceride, cholesterol, and low-density lipoprotein was observed in rabbits consuming a high cholesterol diet (HCD) in addition to H.sabdariffa extract compared to rabbits only fed HCD, suggesting a beneficial effect.[16] Furthermore, the H. sabdariffa seed is abundant in phytosterol and tocopherol, plant forms of cholesterol that have antioxidant and LDL cholesterol lowering effects.
Precautions and Contraindications:
Pregnancy and Lactation
While the mechanism is not well understood, previous animal studies have demonstrated both an inhibitory effect of H. sabdariffa on muscle tone and the anti-fertility effects of Hibiscus rosa-sinensis, respectively. The extract of H. sabdariffa has been shown to stimulate contraction of the rat bladder and uterus; the H.rosa-sinensis extract has exhibited contraceptive effects in the form of estrogen activity in rats. These findings have not been observed in humans. The Hibiscus rosa-sinensis is also thought to have emmenagogue effects which can stimulate menstruation and, in some women, cause an abortion. Due to the documented adverse effects in animal studies and the reported pharmacological properties, the H. sabdariffa and H.rosa-sinensis are not recommended for use during pregnancy. Additionally, they are not recommended while breastfeeding due to the lack of reliable information on its safety and use.
Contraindications
No contraindications have been identified.
Adverse Effects
Drug Interactions
It is postulated that H. sabdariffa interacts with diclofenac, chloroquine and acetaminophen by altering the pharmacokinetics. In healthy human volunteers, the H. sabdariffa extract was found to reduce the excretion of diclofenac upon co-administration. Additionally, co-administration of Karkade (H. sabdariffa), a common Sudanese beverage, was found to reduce chloroquine bioavailability. However, no statistically significant changes were observed in the pharmacokinetics of acetaminophen when administered with the Zobo (H.sabdariffa) drink. Further studies are needed to demonstrate clinical significance.
Species:
In temperate zones, probably the most commonly grown ornamental species is Hibiscus syriacus, the common garden hibiscus, also known in some areas as the "Rose of Althea" or "Rose of Sharon" (but not to be confused with the unrelated Hypericum calycinum, also called "Rose of Sharon"). In tropical and subtropical areas, the Chinese hibiscus (H. rosa-sinensis), with its many showy hybrids, is the most popular hibiscus.
Several hundred species are known, including:
Hibiscis acapulcensis
Hibiscus acetosella Welw. ex Hiern.—False Roselle
Hibiscus acicularis
Hibiscus aculeatus—Comfortroot
Hibiscus altissimus
Hibiscus andongensis
Hibiscus angolensis
Hibiscus aponeurus[26]
Hibiscus archeri—Archer's Hibiscus
Hibiscus aridicola
Hibiscus arnottianus A.Gray—Kokiʻo ʻula (Hawaii)
Hibiscus asper—Bush Roselle
Hibiscus austroyunnanensis
Hibiscus barbosae
Hibiscus benguellensis
Hibiscus berberidifolius
Hibiscus bernieri
Hibiscus bifurcatus—Fork-bracted Rosemallow
Hibiscus biseptus—Arizona Rosemallow
Hibiscus bojerianus
Hibiscus boryanus—Foulsapate Marron
Hibiscus brackenridgei A.Gray—Hawaiian hibiscus Maʻo hau hele
Hibiscus burtt-davyi
Hibiscus caerulescens
Hibiscus caesius—Dark-eyed Hibiscus (South Africa)
Hibiscus calyphyllus—Lemonyellow Rosemallow (Tropical Africa)
Hibiscus cameronii—Cameron's Hibiscus, Pink Hibiscus
Hibiscus cannabinus L.—Kenaf
Hibiscus castroi
Hibiscus cisplatinus—Rosa Del Rio
Hibiscus citrinus-
Hibiscus clayi O.Deg. & I.Deg.—Hawaiian red hibiscus (Hawaii)
Hibiscus clypeatus—Congo Mahoe
Hibiscus coccineus (Medik.) Walter—Scarlet Rosemallow
Hibiscus colimensis
Hibiscus columnaris—Mahot Rempart
Hibiscus comoensis
Hibiscus congestiflorus
Hibiscus costatus
Hibiscus coulteri—Desert Rosemallow
Hibiscus cuanzensis
Hibiscus dasycalyx—Neches River Rosemallow
Hibiscus denudatus Benth.—Pale Face (Southwestern United States, Northwestern Mexico)
Hibiscus dimidiatus
Hibiscus dioscorides A.G.Mill. (es/pt) (Yemen)
Hibiscus diplocrater
Hibiscus diriffan A.G.Mill. (Yemen)
Hibiscus diversifolius—Swamp Hibiscus
Hibiscus dongolensis
Hibiscus donianus
Hibiscus elatus—Mahoe
Hibiscus elegans
Hibiscus engleri—Wild Hibiscus
Hibiscus escobariae
Hibiscus excellii
Hibiscus ferrugineus
Hibiscus ficalhoanus
Hibiscus flavoroseus
Hibiscus fragilis DC.—Mandrinette (Mascarene Islands)
Hibiscus fragrans
Hibiscus fritzscheae
Hibiscus furcellatus Desr.—Lindenleaf rosemallow (Caribbean, Florida, Central America, South America, Hawaii)
Hibiscus fugosioides
Hibiscus furcellatus—Salad Hibiscus
Hibiscus fuscus
Hibiscus genevii Bojer (Mauritius)
Hibiscus gilletii
Hibiscus gossweileri
Hibiscus grandidieri
Hibiscus grandiflorus Michx.—Swamp rosemallow (Southeastern United States)
Hibiscus grandistipulatus
Hibiscus grewiifolius
Hibiscus hamabo
Hibiscus hastatus
Hibiscus heterophyllus—Native rosella
Hibiscus hirtus—Lesser Mallow
Hibiscus hispidissimus
Hibiscus huellensis
Hibiscus hybridus
Hibiscus indicus
Hibiscus insularis Endl.—Phillip Island hibiscus (Phillip Island)
Hibiscus integrifolius
Hibiscus jaliscensis
Hibiscus kochii
Hibiscus kokio—Red Rosemallow
Hibiscus labordei
Hibiscus laevis All. (=H. militaris)—Halberd-leaved rosemallow (central and eastern North America)
Hibiscus lasiocarpos—Woolly Rosemallow
Hibiscus lasiococcus
Hibiscus lavaterioides
Hibiscus laxiflorus
Hibiscus leptocladus ([Northwest Australia])
Hibiscus leviseminus
Hibiscus lilacinus—Lilac Hibiscus
Hibiscus liliiflorus—Rodrigues Tree Hibiscus
Hibiscus longifolius
Hibiscus longisepalus
Hibiscus ludwigii
Hibiscus lunariifolius
Hibiscus macrogonus
Hibiscus macrophyllus—Largeleaf Rosemallow
Hibiscus macropodus
Hibiscus makinoi—Okinawan Hibiscus
Hibiscus malacophyllus Balf.f. (Yemen)
Hibiscus malacospermus
Hibiscus martianus—Heartleaf Rosemallow
Hibiscus moscheutos Welw. ex Hiern.—Crimsoneyed Rosemallow (Central and Eastern North America)
Hibiscus mutabilis L.—Cotton Rosemallow, Confederate Rose (East Asia)
Hibiscus paramutabilis
Hibiscus pedunculatus
Hibiscus pernambucensis—Seaside Mahoe
Hibiscus phoeniceus—Brazilian Rosemallow
Hibiscus platanifolius
Hibiscus quattenensis
Hibiscus poeppigii—Poeppig's Rosemallow
Hibiscus radiatus—Monarch Rosemallow
Hibiscus rosa-sinensis L.—Chinese hibiscus (East Asia)
Hibiscus sabdariffa L.—Roselle, Omutete, or Sorrel
Hibiscus schizopetalus—Fringed Rosemallow
Hibiscus scottii
Hibiscus socotranus
Hibiscus sinosyriacus
Hibiscus splendens
Hibiscus stenanthus Balf.f. (Yemen)
Hibiscus striatus—Striped Rosemallow
Hibiscus syriacus L. (Type species)—Rose of Sharon (Asia)
Hibiscus tiliaceus L.—Sea hibiscus (Australia, Southeast Asia, Oceania)
Hibiscus trilobus—Threelobe Rosemallow
Hibiscus trionum L.—Flower-of-an-Hour
Hibiscus vitifolius—Tropical Rose Mallow
Hibiscus waimeae A.Heller—Kokiʻo keʻokeʻo (Hawaii)
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn.[5] Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States,[30] Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70%[57] to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn.[91] Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel.[120] When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
Ornamental and other uses
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn.[5] Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States,[30] Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70%[57] to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn.[91] Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel.[120] When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
Ornamental and other uses
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
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This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
Maize (/meɪz/ MAYZ; Zea mays subsp. mays, from Spanish: maíz after Taino: mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. The leafy stalk of the plant produces pollen inflorescences and separate ovuliferous inflorescences called ears that yield kernels or seeds, which are fruits.
Maize has become a staple food in many parts of the world, with the total production of maize surpassing that of wheat or rice. In addition to being consumed directly by humans (often in the form of masa), maize is also used for corn ethanol, animal feed and other maize products, such as corn starch and corn syrup. The six major types of maize are dent corn, flint corn, pod corn, popcorn, flour corn, and sweet corn. Sugar-rich varieties called sweet corn are usually grown for human consumption as kernels, while field corn varieties are used for animal feed, various corn-based human food uses (including grinding into cornmeal or masa, pressing into corn oil, and fermentation and distillation into alcoholic beverages like bourbon whiskey), and as chemical feedstocks. Maize is also used in making ethanol and other biofuels.
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2014, total world production was 1.04 billion tonnes. Maize is the most widely grown grain crop throughout the Americas, with 361 million metric tons grown in the United States alone in 2014. Genetically modified maize made up 85% of the maize planted in the United States in 2009. Subsidies in the United States help to account for its high level of cultivation of maize and its position as the largest producer in the world.
HISTORY
PRE-COLUMBIAN DEVELOPMENT
Maize is a cultigen; human intervention is required for it to propagate. Whether or not the kernels fall off the cob on their own is a key piece of evidence used in archaeology to distinguish domesticated maize from its naturally-propagating teosinte ancestor. Genetic evidence can also be used to determine when various lineages split.
Most historians believe maize was domesticated in the Tehuacán Valley of Mexico. Recent research in the early 21st century has modified this view somewhat; scholars now indicate the adjacent Balsas River Valley of south-central Mexico as the center of domestication.
An influential 2002 study by Matsuoka et al. has demonstrated that, rather than the multiple independent domestications model, all maize arose from a single domestication in southern Mexico about 9,000 years ago. The study also demonstrated that the oldest surviving maize types are those of the Mexican highlands. Later, maize spread from this region over the Americas along two major paths. This is consistent with a model based on the archaeological record suggesting that maize diversified in the highlands of Mexico before spreading to the lowlands.
Archaeologist Dolores Piperno has said:
A large corpus of data indicates that [maize] was dispersed into lower Central America by 7600 BP [5600 BC] and had moved into the inter-Andean valleys of Colombia between 7000 and 6000 BP [5000–4000 BC].
— Dolores Piperno, The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments
Since then, even earlier dates have been published.
According to a genetic study by Embrapa, corn cultivation was introduced in South America from Mexico, in two great waves: the first, more than 6000 years ago, spread through the Andes. Evidence of cultivation in Peru has been found dating to about 6700 years ago. The second wave, about 2000 years ago, through the lowlands of South America.
The earliest maize plants grew only small, 25-millimetre-long (1 in) corn cobs, and only one per plant. In Jackson Spielvogel's view, many centuries of artificial selection (rather than the current view that maize was exploited by interplanting with teosinte) by the indigenous people of the Americas resulted in the development of maize plants capable of growing several cobs per plant, which were usually several centimetres/inches long each. The Olmec and Maya cultivated maize in numerous varieties throughout Mesoamerica; they cooked, ground and processed it through nixtamalization. It was believed that beginning about 2500 BC, the crop spread through much of the Americas. Research of the 21st century has established even earlier dates. The region developed a trade network based on surplus and varieties of maize crops.
Mapuches of south-central Chile cultivated maize along with quinoa and potatoes in pre-Hispanic times; however, potato was the staple food of most Mapuches, "specially in the southern and coastal [Mapuche] territories where maize did not reach maturity". Before the expansion of the Inca Empire maize was traded and transported as far south as 40°19' S in Melinquina, Lácar Department. In that location maize remains were found inside pottery dated to 730 ± 80 BP and 920 ± 60 BP. Probably this maize was brought across the Andes from Chile. The presence of maize in Guaitecas Archipelago (43°55' S), the southernmost outpost of pre-Hispanic agriculture, is reported by early Spanish explorers. However the Spanish may have misidentified the plant.
COLUMBIAN EXCHANGE
After the arrival of Europeans in 1492, Spanish settlers consumed maize, and explorers and traders carried it back to Europe and introduced it to other countries. Spanish settlers far preferred wheat bread to maize, cassava, or potatoes. Maize flour could not be substituted for wheat for communion bread, since in Christian belief only wheat could undergo transubstantiation and be transformed into the body of Christ. Some Spaniards worried that by eating indigenous foods, which they did not consider nutritious, they would weaken and risk turning into Indians. "In the view of Europeans, it was the food they ate, even more than the environment in which they lived, that gave Amerindians and Spaniards both their distinctive physical characteristics and their characteristic personalities." Despite these worries, Spaniards did consume maize. Archeological evidence from Florida sites indicate they cultivated it as well.
Maize spread to the rest of the world because of its ability to grow in diverse climates. It was cultivated in Spain just a few decades after Columbus's voyages and then spread to Italy, West Africa and elsewhere. Widespread cultivation most likely began in southern Spain in 1525, after which it quickly spread to the rest of the Spanish Empire including its territories in Italy (and, from there, to other Italian states). Maize had many advantages over wheat and barley; it yielded two and a half times the food energy per unit cultivated area, could be harvested in successive years from the same plot of land, and grew in wildly varying altitudes and climates, from relatively dry regions with only 250 mm (10 in) of annual rainfall to damp regions with over 5,000 mm (200 in). By the 17th century it was a common peasant food in Southwestern Europe, including Portugal, Spain, southern France, and Italy. By the 18th century, it was the chief food of the southern French and Italian peasantry, especially in the form of polenta in Italy.
Names
The word maize derives from the Spanish form of the indigenous Taíno word for the plant, mahiz. It is known by other names around the world.
The word "corn" outside the US, Canada, Australia, and New Zealand refers to any cereal crop, its meaning understood to vary geographically to refer to the local staple. In the United States, Canada, Australia, and New Zealand, corn primarily means maize; this usage started as a shortening of "Indian corn". "Indian corn" primarily means maize (the staple grain of indigenous Americans), but can refer more specifically to multicolored "flint corn" used for decoration.
In places outside the US, Canada, Australia, and New Zealand, corn often refers to maize in culinary contexts. The narrower meaning is usually indicated by some additional word, as in sweet corn, sweetcorn, corn on the cob, baby corn, the puffed confection known as popcorn and the breakfast cereal known as corn flakes.
In Southern Africa, maize is commonly called mielie (Afrikaans) or mealie (English), words derived from the Portuguese word for maize, milho.
Maize is preferred in formal, scientific, and international usage because it refers specifically to this one grain, unlike corn, which has a complex variety of meanings that vary by context and geographic region. Maize is used by agricultural bodies and research institutes such as the FAO and CSIRO. National agricultural and industry associations often include the word maize in their name even in English-speaking countries where the local, informal word is something other than maize; for example, the Maize Association of Australia, the Indian Maize Development Association, the Kenya Maize Consortium and Maize Breeders Network, the National Maize Association of Nigeria, the Zimbabwe Seed Maize Association.
STRUCTURE AND PHYSIOLOGY
The maize plant is often 3 m (10 ft) in height, though some natural strains can grow 13 m (43 ft). The stem is commonly composed of 20 internodes of 18 cm (7 in) length. The leaves arise from the nodes, alternately on opposite sides on the stalk. A leaf, which grows from each node, is generally 9 cm (3+1⁄2 in) in width and 120 cm (3 ft 11 in) in length.
Ears develop above a few of the leaves in the midsection of the plant, between the stem and leaf sheath, elongating by around 3 mm (1⁄8 in) per day, to a length of 18 cm (7 in) with 60 cm (24 in) being the maximum alleged in the subspecies. They are female inflorescences, tightly enveloped by several layers of ear leaves commonly called husks. Certain varieties of maize have been bred to produce many additional developed ears. These are the source of the "baby corn" used as a vegetable in Asian cuisine.
The apex of the stem ends in the tassel, an inflorescence of male flowers. When the tassel is mature and conditions are suitably warm and dry, anthers on the tassel dehisce and release pollen. Maize pollen is anemophilous (dispersed by wind), and because of its large settling velocity, most pollen falls within a few meters of the tassel.
Elongated stigmas, called silks, emerge from the whorl of husk leaves at the end of the ear. They are often pale yellow and 18 cm (7 in) in length, like tufts of hair in appearance. At the end of each is a carpel, which may develop into a "kernel" if fertilized by a pollen grain. The pericarp of the fruit is fused with the seed coat referred to as "caryopsis", typical of the grasses, and the entire kernel is often referred to as the "seed". The cob is close to a multiple fruit in structure, except that the individual fruits (the kernels) never fuse into a single mass. The grains are about the size of peas, and adhere in regular rows around a white, pithy substance, which forms the ear. The maximum size of kernels is reputedly 2.5 cm (1 in). An ear commonly holds 600 kernels. They are of various colors: blackish, bluish-gray, purple, green, red, white and yellow. When ground into flour, maize yields more flour with much less bran than wheat does. It lacks the protein gluten of wheat and, therefore, makes baked goods with poor rising capability. A genetic variant that accumulates more sugar and less starch in the ear is consumed as a vegetable and is called sweet corn. Young ears can be consumed raw, with the cob and silk, but as the plant matures (usually during the summer months), the cob becomes tougher and the silk dries to inedibility. By the end of the growing season, the kernels dry out and become difficult to chew without cooking them tender first in boiling water.
Planting density affects multiple aspects of maize. Modern farming techniques in developed countries usually rely on dense planting, which produces one ear per stalk. Stands of silage maize are yet denser,[citation needed] and achieve a lower percentage of ears and more plant matter.
Maize is a facultative short-day plant and flowers in a certain number of growing degree days > 10 °C (50 °F) in the environment to which it is adapted. The magnitude of the influence that long nights have on the number of days that must pass before maize flowers is genetically prescribed and regulated by the phytochrome system.
Photoperiodicity can be eccentric in tropical cultivars such that the long days characteristic of higher latitudes allow the plants to grow so tall that they do not have enough time to produce seed before being killed by frost. These attributes, however, may prove useful in using tropical maize for biofuels.
Immature maize shoots accumulate a powerful antibiotic substance, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA). DIMBOA is a member of a group of hydroxamic acids (also known as benzoxazinoids) that serve as a natural defense against a wide range of pests, including insects, pathogenic fungi and bacteria. DIMBOA is also found in related grasses, particularly wheat. A maize mutant (bx) lacking DIMBOA is highly susceptible to attack by aphids and fungi. DIMBOA is also responsible for the relative resistance of immature maize to the European corn borer (family Crambidae). As maize matures, DIMBOA levels and resistance to the corn borer decline.
Because of its shallow roots, maize is susceptible to droughts, intolerant of nutrient-deficient soils, and prone to be uprooted by severe winds.
While yellow maizes derive their color from lutein and zeaxanthin, in red-colored maizes, the kernel coloration is due to anthocyanins and phlobaphenes. These latter substances are synthesized in the flavonoids synthetic pathway from polymerization of flavan-4-ols by the expression of maize pericarp color1 (p1) gene which encodes an R2R3 myb-like transcriptional activator of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments, while the P1-wr allele specifies colorless kernel pericarp and red cobs, and unstable factor for orange1 (Ufo1) modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate significant amounts of phlobaphene pigments. The maize P gene encodes a Myb homolog that recognizes the sequence CCT/AACC, in sharp contrast with the C/TAACGG bound by vertebrate Myb proteins.
The ear leaf is the leaf most closely associated with a particular developing ear. This leaf and above contribute 70% to 75% to 90% of grain fill. Therefore fungicide application is most important in that region in most disease environments.
ABNORMAL FLOWERS
Maize flowers may sometimes exhibit mutations that lead to the formation of female flowers in the tassel. These mutations, ts4 and Ts6, prohibit the development of the stamen while simultaneously promoting pistil development. This may cause inflorescences containing both male and female flowers, or hermaphrodite flowers.
GENETICS
Maize is an annual grass in the family Gramineae, which includes such plants as wheat, rye, barley, rice, sorghum, and sugarcane. There are two major species of the genus Zea (out of six total): Zea mays (maize) and Zea diploperennis, which is a perennial type of teosinte. The annual teosinte variety called Zea mays mexicana is the closest botanical relative to maize. It still grows in the wild as an annual in Mexico and Guatemala.
Many forms of maize are used for food, sometimes classified as various subspecies related to the amount of starch each has:
Flour corn: Zea mays var. amylacea
Popcorn: Zea mays var. everta
Dent corn : Zea mays var. indentata
Flint corn: Zea mays var. indurata
Sweet corn: Zea mays var. saccharata and Zea mays var. rugosa
Waxy corn: Zea mays var. ceratina
Amylomaize: Zea mays
Pod corn: Zea mays var. tunicata Larrañaga ex A. St. Hil.
Striped maize: Zea mays var. japonica
This system has been replaced (though not entirely displaced) over the last 60 years by multivariable classifications based on ever more data. Agronomic data were supplemented by botanical traits for a robust initial classification, then genetic, cytological, protein and DNA evidence was added. Now, the categories are forms (little used), races, racial complexes, and recently branches.
Maize is a diploid with 20 chromosomes (n=10). The combined length of the chromosomes is 1500 cM. Some of the maize chromosomes have what are known as "chromosomal knobs": highly repetitive heterochromatic domains that stain darkly. Individual knobs are polymorphic among strains of both maize and teosinte.
Barbara McClintock used these knob markers to validate her transposon theory of "jumping genes", for which she won the 1983 Nobel Prize in Physiology or Medicine. Maize is still an important model organism for genetics and developmental biology today.
The centromeres have two types of structural components, both of which are found only in the centromeres: Large arrays of CentC, a short satellite DNA; and a few of a family of retrotransposons. The B chromosome, unlike the others, contains an additional repeat which extends into neighboring areas of the chromosome. Centromeres can accidentally shrink during division and still function, although it is thought this will fail if it shrinks below a few hundred kilobase. Kinetochores contain RNA originating from centromeres. Centromere regions can become inactive, and can continue in that state if the chromosome still has another active one.
The Maize Genetics Cooperation Stock Center, funded by the USDA Agricultural Research Service and located in the Department of Crop Sciences at the University of Illinois at Urbana-Champaign, is a stock center of maize mutants. The total collection has nearly 80,000 samples. The bulk of the collection consists of several hundred named genes, plus additional gene combinations and other heritable variants. There are about 1000 chromosomal aberrations (e.g., translocations and inversions) and stocks with abnormal chromosome numbers (e.g., tetraploids). Genetic data describing the maize mutant stocks as well as myriad other data about maize genetics can be accessed at MaizeGDB, the Maize Genetics and Genomics Database.
In 2005, the US National Science Foundation (NSF), Department of Agriculture (USDA) and the Department of Energy (DOE) formed a consortium to sequence the B73 maize genome. The resulting DNA sequence data was deposited immediately into GenBank, a public repository for genome-sequence data. Sequences and genome annotations have also been made available throughout the project's lifetime at the project's official site.
Primary sequencing of the maize genome was completed in 2008. On November 20, 2009, the consortium published results of its sequencing effort in Science. The genome, 85% of which is composed of transposons, was found to contain 32,540 genes (By comparison, the human genome contains about 2.9 billion bases and 26,000 genes). Much of the maize genome has been duplicated and reshuffled by helitrons—group of rolling circle transposons.
In Z. mays and various other angiosperms the MADS-box motif is involved in floral development. Early study in several angiosperm models including Z. mays was the beginning of research into the molecular evolution of floral structure in general, as well as their role in nonflowering plants.
EVOLUTION
As with many plants and animals, Z. mays has a positive correlation between effective population size and the magnitude of selection pressure. Z. m. having an EPS of ~650,000, it clusters with others of about the same EPS, and has 79% of its amino acid sites under selection.
Recombination is a significant source of diversity in Z. mays. (Note that this finding supersedes previous studies which showed no such correlation.)
This recombination/diversity effect is seen throughout plants but is also found to not occur – or not as strongly – in regions of high gene density. This is likely the reason that domesticated Z. mays has not seen as much of an increase in diversity within areas of higher density as in regions of lower density, although there is more evidence in other plants.
Some lines of maize have undergone ancient polyploidy events, starting 11m years ago. Over that time ~72% of polyploid duplicated genes have been retained, which is higher than other plants with older polyploidy events. Thus maize may be due to lose more duplicate genes as time goes along, similar to the course followed by the genomes of other plants. If so - if gene loss has merely not occurred yet - that could explain the lack of observed positive selection and lower negative selection which are observed in otherwise similar plants, i.e. also naturally outcrossing and with similar effective population sizes.
Ploidy does not appear to influence EPS or magnitude of selection effect in maize.
BREEDING
Maize reproduces sexually each year. This randomly selects half the genes from a given plant to propagate to the next generation, meaning that desirable traits found in the crop (like high yield or good nutrition) can be lost in subsequent generations unless certain techniques are used.
Maize breeding in prehistory resulted in large plants producing large ears. Modern breeding began with individuals who selected highly productive varieties in their fields and then sold seed to other farmers. James L. Reid was one of the earliest and most successful developing Reid's Yellow Dent in the 1860s. These early efforts were based on mass selection. Later breeding efforts included ear to row selection (C. G. Hopkins c. 1896), hybrids made from selected inbred lines (G. H. Shull, 1909), and the highly successful double cross hybrids using four inbred lines (D. F. Jones c. 1918, 1922). University supported breeding programs were especially important in developing and introducing modern hybrids. By the 1930s, companies such as Pioneer devoted to production of hybrid maize had begun to influence long-term development. Internationally important seed banks such as the International Maize and Wheat Improvement Center (CIMMYT) and the US bank at the Maize Genetics Cooperation Stock Center University of Illinois at Urbana-Champaign maintain germplasm important for future crop development.
Since the 1940s the best strains of maize have been first-generation hybrids made from inbred strains that have been optimized for specific traits, such as yield, nutrition, drought, pest and disease tolerance. Both conventional cross-breeding and genetic modification have succeeded in increasing output and reducing the need for cropland, pesticides, water and fertilizer. There is conflicting evidence to support the hypothesis that maize yield potential has increased over the past few decades. This suggests that changes in yield potential are associated with leaf angle, lodging resistance, tolerance of high plant density, disease/pest tolerance, and other agronomic traits rather than increase of yield potential per individual plant.
Tropical landraces remain an important and underutilized source of resistance alleles for for disease and for herbivores. Notable discoveries of rare alleles for this purpose were made by Dao et al 2014 and Sood et al 2014.
GLOBAL PROGRAM
CIMMYT operates a conventional breeding program to provide optimized strains. The program began in the 1980s. Hybrid seeds are distributed in Africa by the Drought Tolerant Maize for Africa project.
GENETIC MODIFICATION
Genetically modified (GM) maize was one of the 26 GM crops grown commercially in 2016. The vast majority of this is Bt maize. Grown since 1997 in the United States and Canada, 92% of the US maize crop was genetically modified in 2016 and 33% of the worldwide maize crop was GM in 2016. As of 2011, Herbicide-tolerant maize varieties were grown in Argentina, Australia, Brazil, Canada, China, Colombia, El Salvador, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, the Russian Federation, Singapore, South Africa, Taiwan, Thailand, and the United States. Insect-resistant maize was grown in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Egypt, the European Union, Honduras, Japan, Korea, Malaysia, Mexico, New Zealand, Philippines, South Africa, Switzerland, Taiwan, the United States, and Uruguay.
In September 2000, up to $50 million worth of food products were recalled due to the presence of Starlink genetically modified corn, which had been approved only for animal consumption and had not been approved for human consumption, and was subsequently withdrawn from the market.
ORIGIN
Maize is the domesticated variant of teosinte. The two plants have dissimilar appearance, maize having a single tall stalk with multiple leaves and teosinte being a short, bushy plant. The difference between the two is largely controlled by differences in just two genes, called grassy tillers-1 (gt1, A0A317YEZ1) and teosinte branched-1 (tb1, Q93WI2).
Several theories had been proposed about the specific origin of maize in Mesoamerica:
It is a direct domestication of a Mexican annual teosinte, Zea mays ssp. parviglumis, native to the Balsas River valley in south-eastern Mexico, with up to 12% of its genetic material obtained from Zea mays ssp. mexicana through introgression.
It has been derived from hybridization between a small domesticated maize (a slightly changed form of a wild maize) and a teosinte of section Luxuriantes, either Z. luxurians or Z. diploperennis.
It has undergone two or more domestications either of a wild maize or of a teosinte. (The term "teosinte" describes all species and subspecies in the genus Zea, excluding Zea mays ssp. mays.)
It has evolved from a hybridization of Z. diploperennis by Tripsacum dactyloides.
In the late 1930s, Paul Mangelsdorf suggested that domesticated maize was the result of a hybridization event between an unknown wild maize and a species of Tripsacum, a related genus. This theory about the origin of maize has been refuted by modern genetic testing, which refutes Mangelsdorf's model and the fourth listed above.
The teosinte origin theory was proposed by the Russian botanist Nikolai Ivanovich Vavilov in 1931 and the later American Nobel Prize-winner George Beadle in 1932.: 10 It is supported experimentally and by recent studies of the plants' genomes. Teosinte and maize can cross-breed and produce fertile offspring. A number of questions remain concerning the species, among them:
how the immense diversity of the species of sect. Zea originated,
how the tiny archaeological specimens of 3500–2700 BC could have been selected from a teosinte, and
how domestication could have proceeded without leaving remains of teosinte or maize with teosintoid traits earlier than the earliest known until recently, dating from ca. 1100 BC.
The domestication of maize is of particular interest to researchers—archaeologists, geneticists, ethnobotanists, geographers, etc. The process is thought by some to have started 7,500 to 12,000 years ago. Research from the 1950s to 1970s originally focused on the hypothesis that maize domestication occurred in the highlands between the states of Oaxaca and Jalisco, because the oldest archaeological remains of maize known at the time were found there.
Connection with 'parviglumis' subspecies
Genetic studies, published in 2004 by John Doebley, identified Zea mays ssp. parviglumis, native to the Balsas River valley in Mexico's southwestern highlands, and also known as Balsas teosinte, as being the crop wild relative that is genetically most similar to modern maize. This was confirmed by further studies, which refined this hypothesis somewhat. Archaeobotanical studies, published in 2009, point to the middle part of the Balsas River valley as the likely location of early domestication; this river is not very long, so these locations are not very distant. Stone milling tools with maize residue have been found in an 8,700 year old layer of deposits in a cave not far from Iguala, Guerrero.
Doebley was part of the team that first published, in 2002, that maize had been domesticated only once, about 9,000 years ago, and then spread throughout the Americas.
A primitive corn was being grown in southern Mexico, Central America, and northern South America 7,000 years ago. Archaeological remains of early maize ears, found at Guila Naquitz Cave in the Oaxaca Valley, date back roughly 6,250 years; the oldest ears from caves near Tehuacan, Puebla, 5,450 B.P.
Maize pollen dated to 7,300 B.P. from San Andres, Tabasco, on the Caribbean coast has also been recovered.
As maize was introduced to new cultures, new uses were developed and new varieties selected to better serve in those preparations. Maize was the staple food, or a major staple – along with squash, Andean region potato, quinoa, beans, and amaranth – of most pre-Columbian North American, Mesoamerican, South American, and Caribbean cultures. The Mesoamerican civilization, in particular, was deeply interrelated with maize. Its traditions and rituals involved all aspects of maize cultivation – from the planting to the food preparation. Maize formed the Mesoamerican people's identity.
It is unknown what precipitated its domestication, because the edible portion of the wild variety is too small, and hard to obtain, to be eaten directly, as each kernel is enclosed in a very hard bivalve shell.
In 1939, George Beadle demonstrated that the kernels of teosinte are readily "popped" for human consumption, like modern popcorn. Some have argued it would have taken too many generations of selective breeding to produce large, compressed ears for efficient cultivation. However, studies of the hybrids readily made by intercrossing teosinte and modern maize suggest this objection is not well founded.
SPREADING TO THE NORTH
Around 4,500 ago, maize began to spread to the north; it was first cultivated in what is now the United States at several sites in New Mexico and Arizona, about 4,100 ago.
During the first millennium AD, maize cultivation spread more widely in the areas north. In particular, the large-scale adoption of maize agriculture and consumption in eastern North America took place about A.D. 900. Native Americans cleared large forest and grassland areas for the new crop.
In 2005, research by the USDA Forest Service suggested that the rise in maize cultivation 500 to 1,000 years ago in what is now the southeastern United States corresponded with a decline of freshwater mussels, which are very sensitive to environmental changes.
CULTIVATION
PLANTING
Because it is cold-intolerant, in the temperate zones maize must be planted in the spring. Its root system is generally shallow, so the plant is dependent on soil moisture. As a plant that uses C4 carbon fixation, maize is a considerably more water-efficient crop than plants that use C3 carbon fixation such as alfalfa and soybeans. Maize is most sensitive to drought at the time of silk emergence, when the flowers are ready for pollination. In the United States, a good harvest was traditionally predicted if the maize was "knee-high by the Fourth of July", although modern hybrids generally exceed this growth rate. Maize used for silage is harvested while the plant is green and the fruit immature. Sweet corn is harvested in the "milk stage", after pollination but before starch has formed, between late summer and early to mid-autumn. Field maize is left in the field until very late in the autumn to thoroughly dry the grain, and may, in fact, sometimes not be harvested until winter or even early spring. The importance of sufficient soil moisture is shown in many parts of Africa, where periodic drought regularly causes maize crop failure and consequent famine. Although it is grown mainly in wet, hot climates, it has been said to thrive in cold, hot, dry or wet conditions, meaning that it is an extremely versatile crop.
Maize was planted by the Native Americans in hills, in a complex system known to some as the Three Sisters. Maize provided support for beans, and the beans provided nitrogen derived from nitrogen-fixing rhizobia bacteria which live on the roots of beans and other legumes; and squashes provided ground cover to stop weeds and inhibit evaporation by providing shade over the soil. This method was replaced by single species hill planting where each hill 60–120 cm (2 ft 0 in–3 ft 11 in) apart was planted with three or four seeds, a method still used by home gardeners. A later technique was "checked maize", where hills were placed
1 m (40 in) apart in each direction, allowing cultivators to run through the field in two directions. In more arid lands, this was altered and seeds were planted in the bottom of 10–12 cm (4–4+1⁄2 in) deep furrows to collect water. Modern technique plants maize in rows which allows for cultivation while the plant is young, although the hill technique is still used in the maize fields of some Native American reservations. When maize is planted in rows, it also allows for planting of other crops between these rows to make more efficient use of land space.
In most regions today, maize grown in residential gardens is still often planted manually with a hoe, whereas maize grown commercially is no longer planted manually but rather is planted with a planter. In North America, fields are often planted in a two-crop rotation with a nitrogen-fixing crop, often alfalfa in cooler climates and soybeans in regions with longer summers. Sometimes a third crop, winter wheat, is added to the rotation.
Many of the maize varieties grown in the United States and Canada are hybrids. Often the varieties have been genetically modified to tolerate glyphosate or to provide protection against natural pests. Glyphosate is an herbicide which kills all plants except those with genetic tolerance. This genetic tolerance is very rarely found in nature.
In the midwestern United States, low-till or no-till farming techniques are usually used. In low-till, fields are covered once, maybe twice, with a tillage implement either ahead of crop planting or after the previous harvest. The fields are planted and fertilized. Weeds are controlled through the use of herbicides, and no cultivation tillage is done during the growing season. This technique reduces moisture evaporation from the soil, and thus provides more moisture for the crop. The technologies mentioned in the previous paragraph enable low-till and no-till farming. Weeds compete with the crop for moisture and nutrients, making them undesirable.
HARVESTING
Before the 20th century, all maize harvesting was by manual labour, by grazing, or by some combination of those. Whether the ears were hand-picked and the stover was grazed, or the whole plant was cut, gathered, and shocked, people and livestock did all the work. Between the 1890s and the 1970s, the technology of maize harvesting expanded greatly. Today, all such technologies, from entirely manual harvesting to entirely mechanized, are still in use to some degree, as appropriate to each farm's needs, although the thoroughly mechanized versions predominate, as they offer the lowest unit costs when scaled to large farm operations. For small farms, their unit cost can be too high, as their higher fixed cost cannot be amortized over as many units.[citation needed]
Before World War II, most maize in North America was harvested by hand. This involved a large number of workers and associated social events (husking or shucking bees). From the 1890s onward, some machinery became available to partially mechanize the processes, such as one- and two-row mechanical pickers (picking the ear, leaving the stover) and corn binders, which are reaper-binders designed specifically for maize (for example, Video on YouTube). The latter produce sheaves that can be shocked. By hand or mechanical picker, the entire ear is harvested, which then requires a separate operation of a maize sheller to remove the kernels from the ear. Whole ears of maize were often stored in corn cribs, and these whole ears are a sufficient form for some livestock feeding use. Today corn cribs with whole ears, and corn binders, are less common because most modern farms harvest the grain from the field with a combine and store it in bins. The combine with a corn head (with points and snap rolls instead of a reel) does not cut the stalk; it simply pulls the stalk down. The stalk continues downward and is crumpled into a mangled pile on the ground, where it usually is left to become organic matter for the soil. The ear of maize is too large to pass between slots in a plate as the snap rolls pull the stalk away, leaving only the ear and husk to enter the machinery. The combine separates the husk and the cob, keeping only the kernels.
When maize is a silage crop, the entire plant is usually chopped at once with a forage harvester (chopper) and ensiled in silos or polymer wrappers. Ensiling of sheaves cut by a corn binder was formerly common in some regions but has become uncommon. For storing grain in bins, the moisture of the grain must be sufficiently low to avoid spoiling. If the moisture content of the harvested grain is too high, grain dryers are used to reduce the moisture content by blowing heated air through the grain. This can require large amounts of energy in the form of combustible gases (propane or natural gas) and electricity to power the blowers.
PRODUCTION
Maize is widely cultivated throughout the world, and a greater weight of maize is produced each year than any other grain. In 2018, total world production was 1.15 billion tonnes, led by the United States with 34.2% of the total (table). China produced 22.4% of the global total.
UNITED STATES
In 2016, maize production was forecast to be over 380 million metric tons (15 billion bushels), an increase of 11% over 2014 American production. Based on conditions as of August 2016, the expected yield would be the highest ever for the United States. The area of harvested maize was forecast to be 35 million hectares (87 million acres), an increase of 7% over 2015. Maize is especially popular in Midwestern states such as Indiana, Iowa, and Illinois; in the latter, it was named the state's official grain in 2017.
STORAGE
Drying is vital to prevent or at least reduce mycotoxin contamination. Aspergillus and Fusarium spp. are the most common mycotoxin sources, but there are others. Altogether maize contaminants are so common, and this crop is so economically important, that maize mycotoxins are among the most important in agriculture in general.
USES
HUMAN FOOD
Maize and cornmeal (ground dried maize) constitute a staple food in many regions of the world. Maize is used to produce cornstarch, a common ingredient in home cooking and many industrialized food products. Maize starch can be hydrolyzed and enzymatically treated to produce syrups, particularly high fructose corn syrup, a sweetener; and also fermented and distilled to produce grain alcohol. Grain alcohol from maize is traditionally the source of Bourbon whiskey. Corn flour is used to make cornbread and other baked products.
In prehistoric times Mesoamerican women used a metate to process maize into ground cornmeal, allowing the preparation of foods that were more calorie dense than popcorn. After ceramic vessels were invented the Olmec people began to cook maize together with beans, improving the nutritional value of the staple meal. Although maize naturally contains niacin, an important nutrient, it was not bioavailable without the process of nixtamalization. The Maya used nixtamal meal to make varieties of porridges and tamales. The process was later used in the cuisine of the American South to prepare corn for grits and hominy.
Maize is a staple of Mexican cuisine. Masa (cornmeal treated with limewater) is the main ingredient for tortillas, atole and many other dishes of Central American food. It is the main ingredient of corn tortilla, tamales, pozole, atole and all the dishes based on them, like tacos, quesadillas, chilaquiles, enchiladas, tostadas and many more. In Mexico the fungus of maize, known as huitlacoche, is considered a delicacy.
Coarse maize meal is made into a thick porridge in many cultures: from the polenta of Italy, the angu of Brazil, the mămăligă of Romania, to cornmeal mush in the US (or hominy grits in the South) or the food called mieliepap in South Africa and sadza, nshima, ugali and other names in other parts of Africa. Introduced into Africa by the Portuguese in the 16th century, maize has become Africa's most important staple food crop. These are commonly eaten in the Southeastern United States, foods handed down from Native Americans, who called the dish sagamite.
Maize can also be harvested and consumed in the unripe state, when the kernels are fully grown but still soft. Unripe maize must usually be cooked to become palatable; this may be done by simply boiling or roasting the whole ears and eating the kernels right off the cob. Sweet corn, a genetic variety that is high in sugars and low in starch, is usually consumed in the unripe state. Such corn on the cob is a common dish in the United States, Canada, United Kingdom, Cyprus, some parts of South America, and the Balkans, but virtually unheard of in some European countries. Corn on the cob was hawked on the streets of early 19th-century New York City by poor, barefoot "Hot Corn Girls", who were thus the precursors of hot dog carts, churro wagons, and fruit stands seen on the streets of big cities today.
Within the United States, the usage of maize for human consumption constitutes only around 1/40th of the amount grown in the country. In the United States and Canada, maize is mostly grown to feed livestock, as forage, silage (made by fermentation of chopped green cornstalks), or grain. Maize meal is also a significant ingredient of some commercial animal food products.
NUTRITIONAL VALUE
Raw, yellow, sweet maize kernels are composed of 76% water, 19% carbohydrates, 3% protein, and 1% fat (table). In a 100-gram serving, maize kernels provide 86 calories and are a good source (10–19% of the Daily Value) of the B vitamins, thiamin, niacin (but see Pellagra warning below), pantothenic acid (B5) and folate (right table for raw, uncooked kernels, USDA Nutrient Database). In moderate amounts, they also supply dietary fiber and the essential minerals, magnesium and phosphorus whereas other nutrients are in low amounts (table).
Maize has suboptimal amounts of the essential amino acids tryptophan and lysine, which accounts for its lower status as a protein source. However, the proteins of beans and legumes complement those of maize.
FEED AND FODDER FOR LIVESTOCK
Maize is a major source of both grain feed and fodder for livestock. It is fed to the livestock in various ways. When it is used as a grain crop, the dried kernels are used as feed. They are often kept on the cob for storage in a corn crib, or they may be shelled off for storage in a grain bin. The farm that consumes the feed may produce it, purchase it on the market, or some of both. When the grain is used for feed, the rest of the plant (the corn stover) can be used later as fodder, bedding (litter), or soil amendment. When the whole maize plant (grain plus stalks and leaves) is used for fodder, it is usually chopped all at once and ensilaged, as digestibility and palatability are higher in the ensilaged form than in the dried form. Maize silage is one of the most valuable forages for ruminants. Before the advent of widespread ensilaging, it was traditional to gather the corn into shocks after harvesting, where it dried further. With or without a subsequent move to the cover of a barn, it was then stored for weeks to several months until fed to the livestock. Today ensilaging can occur not only in siloes but also in silage wrappers. However, in the tropics, maize can be harvested year-round and fed as green forage to the animals.
CHEMICALS
Starch from maize can also be made into plastics, fabrics, adhesives, and many other chemical products.
The corn steep liquor, a plentiful watery byproduct of maize wet milling process, is widely used in the biochemical industry and research as a culture medium to grow many kinds of microorganisms.
Chrysanthemin is found in purple corn and is used as a food coloring.
BIO-FUEL
"Feed maize" is being used increasingly for heating; specialized corn stoves (similar to wood stoves) are available and use either feed maize or wood pellets to generate heat. Maize cobs are also used as a biomass fuel source. Maize is relatively cheap and home-heating furnaces have been developed which use maize kernels as a fuel. They feature a large hopper that feeds the uniformly sized maize kernels (or wood pellets or cherry pits) into the fire.[citation needed]
Maize is increasingly used as a feedstock for the production of ethanol fuel. When considering where to construct an ethanol plant, one of the site selection criteria is to ensure there is locally available feedstock. Ethanol is mixed with gasoline to decrease the amount of pollutants emitted when used to fuel motor vehicles. High fuel prices in mid-2007 led to higher demand for ethanol, which in turn led to higher prices paid to farmers for maize. This led to the 2007 harvest being one of the most profitable maize crops in modern history for farmers. Because of the relationship between fuel and maize, prices paid for the crop now tend to track the price of oil.
The price of food is affected to a certain degree by the use of maize for biofuel production. The cost of transportation, production, and marketing are a large portion (80%) of the price of food in the United States. Higher energy costs affect these costs, especially transportation. The increase in food prices the consumer has been seeing is mainly due to the higher energy cost. The effect of biofuel production on other food crop prices is indirect. Use of maize for biofuel production increases the demand, and therefore price of maize. This, in turn, results in farm acreage being diverted from other food crops to maize production. This reduces the supply of the other food crops and increases their prices.
Maize is widely used in Germany as a feedstock for biogas plants. Here the maize is harvested, shredded then placed in silage clamps from which it is fed into the biogas plants. This process makes use of the whole plant rather than simply using the kernels as in the production of fuel ethanol.
A biomass gasification power plant in Strem near Güssing, Burgenland, Austria, began in 2005. Research is being done to make diesel out of the biogas by the Fischer Tropsch method.
Increasingly, ethanol is being used at low concentrations (10% or less) as an additive in gasoline (gasohol) for motor fuels to increase the octane rating, lower pollutants, and reduce petroleum use (what is nowadays also known as "biofuels" and has been generating an intense debate regarding the human beings' necessity of new sources of energy, on the one hand, and the need to maintain, in regions such as Latin America, the food habits and culture which has been the essence of civilizations such as the one originated in Mesoamerica; the entry, January 2008, of maize among the commercial agreements of NAFTA has increased this debate, considering the bad labor conditions of workers in the fields, and mainly the fact that NAFTA "opened the doors to the import of maize from the United States, where the farmers who grow it receive multimillion-dollar subsidies and other government supports. ... According to OXFAM UK, after NAFTA went into effect, the price of maize in Mexico fell 70% between 1994 and 2001. The number of farm jobs dropped as well: from 8.1 million in 1993 to 6.8 million in 2002. Many of those who found themselves without work were small-scale maize growers."). However, introduction in the northern latitudes of the US of tropical maize for biofuels, and not for human or animal consumption, may potentially alleviate this.
COMMODITY
Maize is bought and sold by investors and price speculators as a tradable commodity using corn futures contracts. These "futures" are traded on the Chicago Board of Trade (CBOT) under ticker symbol C. They are delivered every year in March, May, July, September, and December.
ORNAMENTAL AND OTHER USES
Some forms of the plant are occasionally grown for ornamental use in the garden. For this purpose, variegated and colored leaf forms as well as those with colorful ears are used.
Corncobs can be hollowed out and treated to make inexpensive smoking pipes, first manufactured in the United States in 1869.
An unusual use for maize is to create a "corn maze" (or "maize maze") as a tourist attraction. The idea of a maize maze was introduced by the American Maze Company who created a maze in Pennsylvania in 1993. Traditional mazes are most commonly grown using yew hedges, but these take several years to mature. The rapid growth of a field of maize allows a maze to be laid out using GPS at the start of a growing season and for the maize to grow tall enough to obstruct a visitor's line of sight by the start of the summer. In Canada and the US, these are popular in many farming communities.
Maize kernels can be used in place of sand in a sandboxlike enclosure for children's play.
Stigmas from female maize flowers, popularly called corn silk, are sold as herbal supplements.
Maize is used as a fish bait, called "dough balls". It is particularly popular in Europe for coarse fishing.
Additionally, feed corn is sometimes used by hunters to bait animals such as deer or wild hogs.
UNITED STATES USAGE BREAKDOWN
The breakdown of usage of the 12.1-billion-bushel (307-million-tonne) 2008 US maize crop was as follows, according to the World Agricultural Supply and Demand Estimates Report by the USDA.In the US since 2009/2010, maize feedstock use for ethanol production has somewhat exceeded direct use for livestock feed; maize use for fuel ethanol was 5,130 million bushels (130 million tonnes) in the 2013/2014 marketing year.A fraction of the maize feedstock dry matter used for ethanol production is usefully recovered as DDGS (dried distillers grains with solubles). In the 2010/2011 marketing year, about 29.1 million tonnes of DDGS were fed to US livestock and poultry. Because starch utilization in fermentation for ethanol production leaves other grain constituents more concentrated in the residue, the feed value per kg of DDGS, with regard to ruminant-metabolizable energy and protein, exceeds that of the grain. Feed value for monogastric animals, such as swine and poultry, is somewhat lower than for ruminants.
HAZARDS
PELLAGRA
When maize was first introduced into farming systems other than those used by traditional native-American peoples, it was generally welcomed with enthusiasm for its productivity. However, a widespread problem of malnutrition soon arose wherever maize was introduced as a staple food. This was a mystery, since these types of malnutrition were not normally seen among the indigenous Americans, for whom maize was the principal staple food.
It was eventually discovered that the indigenous Americans had learned to soak maize in alkali — water (the process now known as nixtamalization) — made with ashes and lime (calcium oxide) since at least 1200–1500 BC by Mesoamericans. They did this to liberate the corn hulls, but (unbeknownst to natives or colonists) it coincidentally liberates the B-vitamin niacin, the lack of which was the underlying cause of the condition known as pellagra.
Maize was introduced into the diet of non-indigenous Americans without the necessary cultural knowledge acquired over thousands of years in the Americas. In the late 19th century, pellagra reached epidemic proportions in parts of the southern US, as medical researchers debated two theories for its origin: the deficiency theory (which was eventually shown to be true) said that pellagra was due to a deficiency of some nutrient, and the germ theory said that pellagra was caused by a germ transmitted by stable flies. A third theory, promoted by the eugenicist Charles Davenport, held that people only contracted pellagra if they were susceptible to it due to certain "constitutional, inheritable" traits of the affected individual.
Once alkali processing and dietary variety were understood and applied, pellagra disappeared in the developed world. The development of high lysine maize and the promotion of a more balanced diet have also contributed to its demise. Pellagra still exists today in food-poor areas and refugee camps where people survive on donated maize.
ALLERGY
Maize contains lipid transfer protein, an indigestible protein that survives cooking. This protein has been linked to a rare and understudied allergy to maize in humans. The allergic reaction can cause skin rash, swelling or itching of mucous membranes, diarrhea, vomiting, asthma and, in severe cases, anaphylaxis. It is unclear how common this allergy is in the general population.
MYCOTOXINS
Fungicide application does not reduce fungal growth or mycotoxin dramatically, although it can be a part of a successful reduction strategy. Among the most common toxins are those produced by Aspergillus and Fusarium spp. The most common toxins are aflatoxins, fumonisins, zearalenone, and ochratoxin A. Bt maize discourages insect vectors and by so doing it dramatically reduces concentrations of fumonisins, significantly reduces aflatoxins, but only mildly reduces others.
ART
Maize has been an essential crop in the Andes since the pre-Columbian era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Maize was represented anthropomorphically as well as naturally.
In the United States, maize ears along with tobacco leaves are carved into the capitals of columns in the United States Capitol building. Maize itself is sometimes used for temporary architectural detailing when the intent is to celebrate the fall season, local agricultural productivity and culture. Bundles of dried maize stalks are often displayed along with pumpkins, gourds and straw in autumnal displays outside homes and businesses. A well-known example of architectural use is the Corn Palace in Mitchell, South Dakota, which uses cobs and ears of colored maize to implement a mural design that is recycled annually. Another well-known example is the Field of Corn sculpture in Dublin, Ohio, where hundreds of concrete ears of corn stand in a grassy field.
A maize stalk with two ripe ears is depicted on the reverse of the Croatian 1 lipa coin, minted since 1993.
WIKIPEDIA
Laboratory tests now show soy does not reduce mens testosterone. Soy also does NOT contain estrogen.
It turns out soy only has PHYTOestrogen which is not the human form, it's only the PLANT form which does not have the same effect on humans.
In fact, soy actually BLOCKED female estrogen, real estrogen was found in meat, and men who ate soy had higher testosterone and meat eaters had more female estrogen and had lower testosterone.
Steak and Meat was found to contain quantities of actual female estrogen.
SCIENTIFIC EVIDENCE: SOY DOES NOT HAVE FEMINIZING EFFECTS ON MEN
ANALYSIS: "Soybean isoflavone exposure does not have feminizing effects on men" - NIH National Institute of Health
"Neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone levels. Clinical evidence also indicates that isoflavones have no effect on sperm. There is essentially no evidence from the nine identified clinical studies that soy isoflavone exposure affects estrogen levels in men."
www.ncbi.nlm.nih.gov/pubmed/20378106
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LABORATORY TESTS REVEAL SOY ESTROGEN MYTH IS A HOAX.
PUBMED JOURNAL: "Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men"
"32 reports involving 36 treatment groups and 15 placebo-controlled treatment groups with baseline and ending measures involving soy, isoflavones, genistein, phytoestrogens, red clover, androgens, testosterone, and SHBG, were analyzed. CONCLUSION: The results of this meta-analysis found that neither soy foods nore soy isoflavone supplements alter measures of bioavailable Testosterone concentrations in men. There was no effect.
www.ncbi.nlm.nih.gov/pubmed/19524224
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METASTUDY: REVIEW OF OVER 15 STUDIES SHOW NO ESTROGENIC EFFECT OF SOY ON MEN'S TESTOSTERONE
SCIENCE: "Review finds NO Effect of soy on testosterone" - METAREVIEW STUDY
Despite rumours often spread on the internet, "A review of 15 studies into the influence of soy proteins or isoflavones on male hormones has found No evidence of an estrogen-like effect." These rumours stemmed from a handful of flawed reports. "The authors criticized the studies that reported lowered testosterone levels for their methodology." One of them had only 12 subjects in it. In another, the researchers forgot to include a control, and final readings, rendering their results useless. In another one the entire result was due to just 1 subject. The soy scares were based on this flawed science. It was actually found that Soy does not cause breast cancer, protstate cancer, thyroid problems, infant formula problems, or estrogenic effects, on the contrary "Eating soy demonstrated protection against breast cancer, prostate cancer, and heart disease." Eating Soy was confirmed benficial. For women, children, and indeed men.
www.foodnavigator.com/Science-Nutrition/Review-finds-no-e...
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REVIEW FINDS NO SUCH EFFECT OF SOY ON MEN OR TESTOSTERONE:
NEWS: "Scientific Review finds no effect of soy on testosterone"
By Caroline Scott-Thomas, 30-Jun-2009
"Results suggest that consumption of soy foods or isoflavone supplements would Not result in the adverse effects associated with lower [testosterone] levels." "No significant effects of soy protein or isoflavone intake on T [testosterone] or SHBG [sex hormone-binding globulin] were found." There was no effect of soy on testosterone.
www.foodproductiondaily.com/Quality-Safety/Review-finds-n...
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AMERICAN INSTITUTE FOR CANCER RESEARCH: SOY HAS NO ESTROGEN, SOY ESTROGEN MYTH IS AN UN-SCIENTIFIC HOAX.
AICR: "Men Don't Need to Fear Soy Foods" -American Institute for Cancer Research
It’s no wonder that men who have read the recent stories circulating about soy are confused. Some stories claim that soy foods, such as tofu and soy milk, can lead to breast growth or reduce testosterone levels. Fears that the amount of phytoestrogens in moderate amounts of soy foods could stimulate men’s breast tissue or reduce their testosterone are not based on sound research. A study of children fed soy protein formula for more than six months showed no hormonal effects. A study of men found that the men who ate soy foods twice a day for three months showed NO change in testosterone levels. Soy does not cause prostate cancer, on the contrary, the studies showed eating soy by men was beneficial in lowering the risk of prostate cancer. Men can feel safe.
www.foodconsumer.org/newsite/Nutrition/Food/180820091053_...
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SCIENCE: NOT ONLY DOES SOY *NOT* CONTAIN ESTROGEN, SOY *BLOCKS* ESTROGEN
SCIENCE NEWS: "Soy Phytoestrogens May Block Estrogen Effects"
"Isoflavones may protect against the more powerful estrogen produced by the body." "The addition of high levels of dietary soy isoflavones tended to block estrogen." -Senior investigator J. Mark Cline, D.V.M., Ph.D.
www.sciencedaily.com/releases/2006/01/060115154340.htm
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BODYBUILDING MAGAZINES CONFIRM IT:
MUSCULAR DEVELOPMENT: "SOY PROTEIN HAS NO EFFECT ON TESTOSTERONE LEVELS"
"The meta-analysis examined 47 research reports covering 51 treatment groups. Peer-reviewed studies. The analysis concluded that neither soy protein nor isoflavone supplementation exerted any negative alterations on bioavailable testosterone in males, regardless of research model. Soy did not exert any estrogen-like effects in men, nor any lowering of testosterone levels or other reproductive hormones."
www.musculardevelopment.com/index.php?option=com_content&...
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IRONMAN CONFIRMS: SOY PROTEIN HAS NO EFFECT ON MEN, SOY HAS NO EFFECT ON TESTOSTERONE
IRONMAN MAGAZINE: "Eating soy has No effect on either testosterone or estrogen levels"
"You see the caution on countless Internet sites related to bodybuilding: Avoid eating soy products unless you want to lower your testosterone count. At first glance the dire warnings about soy are plausible...However, actual scientific research found that soy protein and isoflavone intake had No significant effects on testosterone. Neither total nor free testosterone was negatively affected by dietary soy in Any of the studies. None. Also, Studies confirmed Soy has no negative effect on thyroid hormones. Both whey and soy proved superior to casein in aiding muscle protein synthesis in young men. Eating soy will have no effect on either testosterone or estrogen. - STRAIGHT FROM "IRONMAN BODYBUILDING" MAGAZINE
www.ironmanmagazine.com/site/soy-and-your-testosterone/
If you've been on a meat-based diet, you've been eating actual female feminine Estrogen.
Men who eat soy, or who are vegetarian do not have this problem.
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
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This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
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World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
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This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
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World leader, international leader, scientist, medical scientist, virologist, philosopher, thinker, cosmologist, sociologist, and Professor Fangruida
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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References References are made to web resources, and related images are from web resources and related websites.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
Presented to Prof. Dr. C. K. Atal for discovery and validation of world's first bioenhancer Piperine, thereby leading to scientific validation of bioenhancers concept and consequently resulting in development of world's first bioenhanced antitubercular formulation Risorine officially released on world TB day may 2011 by Govt. of India and which was also presented to Philanthropist Mr Bill gates by the Indian Government.
CONTRIBUTIONS IN MEDICINE
REFERENCES-
www.jaim.in/text.asp?2010/1/2/96/65073 www.linknaturalproducts.com/downloads/lnp-digest-v6-2010-.... webcache.googleusercontent.com/search?q=cache:L5kfQKgjkMw... www.herbalnet.org/events.htm www.dailyexcelsior.com/dr-atal-conferred-edpa-award-appre...
www.flickr.com/photos/13059662@N06/13401939445/
HEALTH, MEDICINE, DRUGS, TOXICOLOGY
PHARMACOGNOSY, DRUG RESEARCH, DRUG DISCOVERY, DRUG DEVELOPMENT, NEW CONCEPTS, NEW MECHANISMS OF ACTION OF DRUGS, MEDICINAL PLANTS, AYURVEDA ETC
“It takes more than 10-15 years and approximately 500-600 million dollars to put a new drug into the market. Dr. Atal has provided a basket of drugs, molecules, medical concepts and novel mechanisms of action of drugs for the benefit of patients, researchers and medical community.
1.MEDICAL FRATERNITY AWARDS & HONOURS- drug research and development, medicinal plants research,–details in award section.
A.IMA AWARD- Indian Medical Association Award (IMA- EDB) Chikitsa Seva rattan (ratna) award for bioenhancers.
B.EDPA AWARD of appreciation, 2014.
C.Guest of honor at seminar on Bioenhancers jointly organized by Indian Medical Association (EDB) and East Delhi Physicians association at Delhi.
D.Inaugurated the annual conference, Hematology and blood transfusion at Govt. Medical College, Jammu.
2.OTHER AWARDS(drug development , medicinal plants)
A.Dr. I. C. Chopra Science and Technology award to Dr. Atal for several pioneering drug discoveries and drug development.
B.Professor P. N. Mehra Memorial botany award for plant sciences including work on medicinal plants.
3.AWARD WINNING RURAL HEALTH, NUTRITION, RURAL RESEARCH AND DEVELOPMENT DONE AT RRL
A.FICCI AWARD presented to RRL for rural development projects including work on rural health
B.UN GRANT for rural aquaculture development given to RRL (rural nutrition).
4.MEDICINAL CONSULTANCIES
A.World Health Organization projects in Bangladesh and USA (see toxicology).
B.UNDP projects on medicinal plants in Vietnam.
5.LITERATURE (Serial no 184-211,details in author section) -
A.World reference book on medicinal plants used globally in research institutes/universities
B.Numerous research papers in reputed national & international journals.
6.TOXICOLOGY- INTERNATIONAL AUTHORITY on Crotalaria and its Toxicity in Human Food Chain (Crotalaria Adulteration and Toxicity) and WHO / USA Consultancy
A.Solving the mysterious disease in Sarguja district, Madhya Pradesh, India as crotalaria toxicity.
B.Appointed as consultant by WHO to USA (WHO, PAHO and USFDA) as world authority on Crotalaria and toxicity in human food chain.
C.Published several serial research articles on Crotalaria.
7.PUBLIC & RURAL HEALTH- projects include successful control of external parasites (ectoparasites) like louse control using bio-antiparasitic agents , example-(1975-76) by use of Acorus calamus oil and mustard oil, Guinea worm infection (1976-77) by anti zooplankton measures like introduction of pond fishes in villages which thrive on zooplanktons. Aquaculture (rural supplementation of income and nutrition won the UN grant).
8.WORLD’S FIRST GEOTHERMAL ENERGY BORAX EXTRACTION PLANT (Puga-Ladakh-1976)- world’s highest-factory of its time, first in India and perhaps first and only example in the world to extract borax by innovative use of geothermal energy having medicinal use.
9.INDIA’S FIRST IN DRUGS AND MEDICINE
A.Breakthrough technology in mint - technology for manufacture of bolder crystals of menthol//marc into boards which is used in medical formulations.
B.Xanthotoxin manufacture from two plant sources-(ammi majus & heracleum candicans).
C.Risorine-only Indian drug from India released on world TB day, and presented by Indian government to world dignitary Mr. Bill Gates.
D.Sallaki- the second Indian “single plant based scientifically researched modern drug based on traditional Indian system”.
E.First to introduce / popularize superior imported eucalyptus macrorhynea seeds, a source of Rutin used in medicine.
F.Founder/signatory-CCRAS system of medicine.
10.DISCOVERY OF NEW MECHANISMS OF ACTION IN DRUGS
A.Bioenhancers- they increase blood levels of drug (bioavailability) and drug efficacy (bioefficacy) by inhibiting first pass metabolism and increased absorption of drug. Several more mechanisms have been studied / postulated for this effect.
B.Plant Immunomodulators from Rasayanas - first reporting in science.
11.DISCOVERY OF NOVEL OR BETTER MECHANISMS OF ACTION OF DRUGS- (Drug discovery, mechanisms of action of those drugs and first reporting in science in drugs are overlapping topics) see details in next topic and (Serial no 105-112,first reporting in science)
A.Potassium Embelate (centrally acting non narcotic orally effective analgesic acting on new undiscovered receptors in the brain).
B.Sallaki-Non steroidal anti inflammatory gastro protective plant analgesic (active ingredient Boswellic acid) working through inflammatory pathways (all other existing NSAID drugs are ulcerogenic).
C.Vasicine- bronchodilatory, oxytocic and platelet dysfunction/platelet number corrector actions.
D.Anti urolithiatic drug Debelysin (internationally marketed)-See details below.
E.RLX- Anti inflammatory cum bronchodilator drug. All other asthma drugs are either bronchodilators or else anti-inflammatory drugs.
12.WORLD’S FIRST IN BIOENHANCERS
A.Discovery of world’s first bioenhancer Piperine which is also the world’s first plant based bioenhancer. Research includes first deriving the mechanism of action.
B.First coining of the term Bioavailability enhancers (Bioenhancers).
C.This discovery was proven on world’s first experimentally bioenhanced drugs Sparteine and Vasicine.
D.Published the first scientific evidence based reference on Bioenahncers (IDMA bulletin).
E.This discovery scientifically established a new chapter in medical science.
F.Starting the first bioehnanced antitubercular project which led to development of world’s first bioenhanced antitubercular drug Risorine developed by IIIM Jammu, released by Govt. of India on world TB day 2011 and presented to Mr. Bill Gates of Microsoft.
DETAILED DESCRIPTION
DISCOVERY OF NEW CONCEPTS /FIRST REPORTINGS IN MEDICAL SCIENCE
13.DISCOVERY OF WORLD’S FIRST BIOENHANCER PIPERINE (COMMERCIALISED):
A.PIPERINE is the world’s first proven bioenhancer which was discovered and established by Dr. Atal. Spartine and Vasicine were the first experimental bioenhanced drugs, which established the world’s first bioenhancer concept (See next topic) and which ultimately led to development of world’s first bioenhanced antitubercular formulation Risorine.
B.SIGNIFICANCE OF DISCOVERY OF PIPERINE - It was the first time that a molecule was discovered which could increase the potency of several classes of existing drugs even after being administered at reduced dosed. This made the formulation more effective (bioefficacy) while dose reduction meant reduced cost of drug and reduced side effects of the drug. Prior to this the existing methods were confined to Physical methods only, like micronisation, timed release, site release formulations etc.
C.HISTORY-Bioenhancers were first scientifically documented in 1979 at RRL, Jammu. The reason for arriving at the Bioenhancer hypothesis by Dr. Atal was based on a clue on Trikatu obtained after scrutiny of Ayurvedic handbook compiled by another research institute of CSIR. He observed that a large number (about 75%) of herbal formulations used for a large variety of diseases incorporated Trikatu, or one of the ingredients of Trikatu, namely Piper longum. He posed two questions. What was piper doing in so many formulations? Is it effective against all the illnesses? Since piper cannot be a panacea, so other reasons were thought of and one likely postulation was that it probably increased the potency/ bioavailability of formulations. Further research established the bioenhancer concept. Radiolabelled Vasicine and Spartine which were already being used in other experiments at RRL, were used for bioenhancing experiments, and became the first experimental drugs in the world to be scientifically bioenhanced by Piperine in 1979 at RRL, which established the concept. Subsequently several other classes of drugs were also bioenhanced successfully, research papers were published by RRL , Piperine was patented internationally, research scholars were granted doctorate degrees on bioenhancer research and drug development project on anti tubercular formulation was initiated at RRL. With further research by others, bioavailability enhancers were renamed bioenhancers in short, because research has indicated that Piperine may increase efficacy of drugs due to mechanisms other than increased bioavailability (bioefficacy enhancer + bioavailability enhancer = bioenhancers). About 50 years earlier, Bose in his Pharmacopoea Indica while describing the antiasthmatic activity of Vasaka leaves had made an observation that addition of long pepper to Vasaka increased its efficacy. However, no explanation for this observation was put forth by anyone in science, and it remained an observation overlooked and uninvestigated for about 50 years till the discovery of bioenhancers at RRL, Jammu in 1979 based on a clue from Ayurveda.
14.ESTABLISHING NEW CHAPTER OF BIOENHANCERS IN MEDICINE-
A.NEW CHAPTER IN SCIENCE- With the discovery of Bioenhancer Piperine a new chapter in Medicine was established. The term “Bioavailability enhancers” (later renamed bioenhancers or drug boosters) was first /coined at RRL Jammu. The breakthrough was first published by Dr. Atal in 1979 in IDMA bulletin (Atal. C.K., I.D.M.A. Bull, 1979, 10, 36- “A breakthrough in Drug Bioavailability” – A clue from age old wisdom of Ayurveda”. This term did not exist anywhere in medical treatment, drug industry; textbook or scientific literature till bioavailability enhancer Piperine was discovered and authenticated.
B.SIGNIFICANCE OF DISCOVERY BIOENHANCER CONCEPT -This revolutionary award winning globally recognized breakthrough is a basic discovery which has opened new concept/chapters of Bioenhancers in science in the field of drug bioavailability. As a result, it has opened endless new molecules, drugs, classes of drugs waiting to be bioenhanced and newer bioenhancers waiting to be discovered. Several bioenhancers have been discovered after this discovery, but Piperine still remains the most potent bioenhancer till date. This is also an example of traditional drug influencing multiple classes of modern drugs, nutrients and Xenobiotics. Details are provided at the last page.
C.BENEFITS OF BIOENHANCERS- Bioenhancers act like a catalyst and make the formulations more potent even at lesser dose. Reduced dose also makes the formulation safer, cheaper, and better tolerated by patient, with lesser chance of drug resistance (due to better acceptance, better compliance and increased bioefficacy). Moreover added ecological benefits are due to reduced requirement of raw material needed for plant based drugs, particularly for “less bioavailable” plant based drugs or for rare and scarce plants, example being anti cancer drug Taxol. www.jaim.in/text.asp?2010/1/2/96/65073(J-AIM-journal). docs.google.com/viewer?a=v&q=cache:BULgW-7SSm8J:www.n... ( CSIR newsletter).
15.DRUG DEVELOPMENT PROJECT ON WORLD’ FIRST BIOENHANCED ANTITUBERCULAR DRUG - (Risorine/Kit based on Piperine officially released on World TB day, 2011)- Work was started by Dr. Atal on developing Piperine based antitubercular formulation (reference given below) keeping in mind the dire need of the society . Thereafter the world’s first Piperine bioenhanced anti tubercular formulation Risorine/Risorine kit was developed by CSIR (public private partnership) as a novel safer cheaper TB drug with fewer side effects. It was released on world Tuberculosis day 24th March 2011 in presence of current and former ministers for science and technology, India, Director General CSIR and others at Delhi, India and also presented to Mr. Bill Gates. It is almost 50 long years after which something new has happened in the field of tuberculosis research and treatment. Piperine was extensively investigated, researched and took unusually long time to get the concerned permission for launching it in market as Risorine (company launching in 2009 by Cadila Pharmaceuticals and official CSIR launching on world tuberculosis day 2011).In the meantime keletra (Lopinavir/ritonavir) was discovered and officially launched as bioenhanced antiretroviral drug(US FDA approval in 2000). Thus Risorine became the second officially marketed bioenhanced drug in world after keletra even though Rifampicin was experimentally bioenhanced much earlier. However Risorine is still the world’s first bioenhanced marketed antitubercular drug. For details of the World TB day events, See two links below. Reference- Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis, J Assoc Physicians India. 1985 Mar; 33 (3) : 223-4 www.ncbi.nlm.nih.gov/pubmed/4044481http://pib.nic.in/news... csirindia.wordpress.com/2011/03/26/world-tuberculosis-day... RECOGNITION OF PIPERINE DISCOVERY - Bioenhancer discovery has led to the successful development of world’s first bioenhanced antitubercular drug Risorine in market.
A.Globally recognized and accepted discovery by scientific community, Wide media coverage, DD news coverage of Risorine release, internet reports.
B.Dr. I. C. Chopra award, 2000 given to Dr. Atal for plant based drug discoveries including Piperine.
C.Indian Medical Association’s Chikitsa Seva Rattan (ratna) award, IMA-EDB given to Dr. Atal for bioenhancers.
D.EDPA award of appreciation, 2014 given to Dr. Atal for bioenhancer research.
E.Many Medical Conferences on bioenhancers have been held like the one jointly conducted by Indian Medical association (EDB) and East Delhi Physician association at IMA hall (EDB) on 8th May, 2010.
F.CSIR/Govt. of India’s official launching of bioenhanced Risorine on world TB day, 2011 at Anusandhan Bhawan, Delhi.
G.Presentation of Risorine to visiting dignitary Mr. Bill Gates on world TB day, 2011.
H.IDMA research award 1981-82, discipline Pharmacology, at hotel Centaur, Mumbai (erstwhile Bombay) presented to Dr. Usha Zutshi / J. L. Kaul-on best original research paper on “The impact of Ayurvedic herbals on drug bioavailability” in Indian drugs 1982 Sep vol. 19, pg 476-79.
I.CSIR National Technology award 1993 presented to Dr. Usha Zutshi and Dr. K. L. Bedi, for work on piperine.
J.RRL Jammu alone published more than 25 research papers on Piperine based on 10 PhDs dissertations and doctorate degrees awarded on bioenhancers.
K.Worldwide recognition, research and publication of Piperine and bioenhancers.
16.DISCOVERY OF PLANT BASED IMMUNOMODULATORS (discovered from Rasayanas in Ayurveda and available as formulations in market)-First reported case of plant based immunomodulators from plant sources, discovered from Ayurvedic list of Rasayanas class of drugs, a new concept and a major contribution to science. (Serial no 17,award section-Dr. I. C. Chopra award ).Out of 16 plant drugs, 6 were studied in more detail and thus classified on the type of immune modulation produced, as immunosupressants, immunostimulants and immunocorrecting agents (immunoequiliberating). Example includes Picrorhiza kurroa that went into clinical trials has become a part of numerous modern herbal formulations. Some References - Immunomodulating agents of plant origin. I: Preliminary screening, J Ethnopharmacol. 1986 Nov; 18(2): 133 - 41. C. K. Atal, M. L. Sharma, A. Kaul, A. Khajuria, (See links below and events, CSIR, IIIM , first Dr. I. C. Chopra award)
A.http://www.ncbi.nlm.nih.gov/pubmed/3560991
B.http://www.herbalnet.org/events.htm
17.DEBELYSIN (COMMERCIALISED, INTERNATIONALLY MARKETED) patented renal antilithiatic (lithio-lytic or renal calculi dissolving drugs), based on Dolichos biflora Seeds. Not much is available in allopathic system for renal calculi, although methods exist like surgery, cystoscopic removal, lithotripsy, some uncommon methods to dissolve renal calculi, besides some herbal formulations available in market. Debelysin is a patented, safe, scientifically established drug for renal calculi with an international marketed in Poland, Byelorussia and Ukraine. Reference article -Clinical evaluation of a new antilithiatic drug," Debelysin". T Krzeski, A Borowka, W Gustowski, C.K. Atal, A. Pol J Pharmacol Pharm, 1983 - 35(1):1-6. www.ncbi.nlm.nih.gov/pubmed/6889184
18.ANTIARTHRITIC DRUG SALLAKI – BOSWELLIC ACID AS ACTIVE INGREDIENT- (COMMERCIALISED, INTERNATIONALLY MARKETED)- SECOND HERBAL DRUG IN INDIA- Apart from Rauwolfia discovered by Col. Sir R. N. Chopra in late forties, Sallaki, launched in March 1982, became the second other important scientifically proven major herbal drug based on Indian system of medicine (Ayurvedic and Unani) to formally enter Indian market in five decades post independence ( RRL newsletter April 1982). Belladonna was one more such launch elsewhere but it was not a drug in the true sense because it was launched as tincture for its non specific effects/activity on salivation and pain or else as belladonna plaster for boils which are not “activity” specific. Later Atropine extracted from Belladonna became a pure modern drug. After Rauwolfia, Sallaki was “second” in India for the following reasons. It was the second formally launched “single plant” based drug like Rauwolfia, its alcoholic extract was validated for activity in animals, activity was also established to be equivalent to crude drug, and lastly, its scientific validation in animals was reproducible (reference-Dr.K.L.Bedi). The Dr. I. C. Chopra award, 2000 was given to Dr. C. K. Atal for plant based drug discoveries particularly Sallaki, (See award section and internet link). Sallaki is also successfully marketed internationally, particularly Europe, as a safe, effective antiarthritic drug and the only non steroidal anti-inflammatory drug devoid of gastrointestinal side effects (ulceration) and instead it has gastroprotective action. www.phytomedicinejournal.com/article/S0944-7113%2808%2900... The effects on lipids were also investigated for the first time which was also done by CDRI, Lucknow, which progressed further into anti lipidaemic drug development. Mechanism of cholesterol lowering effect of Salai guggal ex. boswellia serrata roxb - U Zutshi, PG Rao, S Kaur, GB Singh, S Surjeet, CK Atal Indian Journal of Pharmacology – 1986, vol. 18,issue 3,pg 182-183.Sallaki is also reportedly being manufactured by Gufic Company in Uzbekistan and has a reported market in Russia and Europe, especially Germany. Boswellic acid is marketed by other companies like Himalaya (as Shallaki) and Amway. www.ijp-online.com/article.asp?issn=0253-7613;year=1986;v...
19.VASICINE, VASICINONE, AND ITS ANALOGUES (MARKETED AS AYURVEDIC FORMULATIONS) -OFFER OF US DOLLARS 80,000/- FOR INDO-US COLLABORATION ON THIS DRUG-exhibiting bronchodilatory, oxytocic and platelet dysfunction/platelet number corrector actions. Vasicine from Adhatoda vasica was discovered to control capillary bleeding through action on Bone Marrow. Dr. Atal while on a visit to USA in 1981 was offered Indo US collaborative research on vasicine. A provisional agreement was signed in USA with Farmacon dated 29th Oct, 1981, and agreed that the data be provided to Farmacon research Corporation, 39, South Lasalle street , Chicago Illinois, USA for a sum of US dollars eighty thousand(US $ 80,000/-) plus additional negotiable royalty , subject to CSIR Head office approval and retaining justified rights by CSIR. This was meant to be researched further in USA for possible marketing in USA (& Pakistan) as per agreement with Alan J, Schroeder, Vice President of the company. Since approval was delayed so the advance cheque was returned back to the company in USAL. This was the highest ever recorded amount of that time offered to any of the CSIR laboratories from international companies and original signed documents of agreement are still preserved. www.flickr.com/photos/13059662@N06/6506562555/in/photostream
20.RLX-a significant work on bronchodilatory effects of Deoxy vasicinone (RLX). This molecule is a wonderful anti inflammatory bronchodilator with minimal side effects as compared to conventional existing drugs and having a novel mechanism of action entirely different from others. The existing anti asthmatic drugs possesses either anti-inflammatory or else bronchodilatory effect, whereas RLX has both the properties.
21.POTASSIUM EMBELLATE-THE ONLY DRUG OF ITS KIND- a centrally acting, non narcotic orally effective analgesic, the only molecule of its kind known to exist. This is new molecule acting on so far unknown and undiscovered receptors in the brain (as peripherally it is devoid of anti-inflammatory action and centrally its effect is not reversed by opioid antagonists suggesting some different site of action/receptors in brain). Reference-
A.http://www.ncbi.nlm.nih.gov/pubmed/2561116
B.http://www.ncbi.nlm.nih.gov/pubmed/6541278
22.HEPATOPROTECTIVE FORMULATIONS (COMMERCIALISED): - significant work on plant based hepatoprotective formulations based on many plants. It was launched in the market as Livzone, a hepatoprotective formulation (Hind Chemicals, Kanpur). www.herbalnet.org/events.htm (CSIR- IIIM , Serial no 17 ,first Dr. I. C. Chopra award)
23.TECHNOLOGY TRANSFER FOR ABOVE DRUGS- Sallaki (Gufic Company, Bombay, renamed Mumbai), Hepatoprotective Livzone (Hind Chemicals, Kanpur under Dr. Rohtagi), Piperine Bioenhanced Anti tubercular formulation Risorine/risorine kit (Cadila Pharmaceuticals, Ahemedabad). Immunomodulator Picrorrhiza is being used in many herbal formulations and so is Vasicine. Antiurolithiatic drug Debelysin has been internationally developed by Herbapol from Poland.
A.DRUGS RESEARCHED IN INDIA- Sallaki, Risorine, Hepatoprotectives (Livzone), RLX, Vasicine, Potassium Embellate
B.DRUGS RESEARCHED INTERNATIONALLY- Debelysin
C.DRUGS COMMERCIALISED IN INDIA- Livzone, Risorine, Sallaki
D.INDIAN DRUG COMMERCIALISED INTERNATIONALLY- Sallaki
E.DRUGS DEVELOPED & COMMERCIALISED INTERNATIONALLY-Debelysin
24.PROCESS DEVELOPED FOR INDIA FOR SEVERAL KNOWN AND EXISTING DRUGS – Phytochemicals (Seventeen) ,Drug Intermediates (Three) ,Fermentation Technology (Four) (for detailed list Serial no 152-159,processes developed for India.Broad categories are Processes for medicinal Essential Oils Isolates(like mint), Phytochemicals, Drugs, Intermediates, Pharmaceuticals, Mineral Products(plaster of Paris), Fermentation Technology Products(citric acid),mint etc used by the Medical profession.
25.CONTRIBUTIONS IN AYURVEDA- All drugs mentioned above in drug discoveries are based on medicinal plants and Ayurvedic/herbal plants (Serial no 201-204, professional standing and peer reviews).
A.Discovery of New Drugs, Concepts and Mechanisms of Action of Drugs from Ayurveda- (Serial no 92-112, drug discovery for details).
B.Significance of Work Done, Visionary Concepts, Recognition in Ayurveda- Details in Professional Standing.
26.RENOWNED INTERNATIONAL AUTHORITY AND CONSULTANT ON MEDICINAL PLANTS (PHARMACOGNOSY)
A.United Nations Consultant-UNDP, UNIDO. USFDA,FAO,WHO Etc
B.Consultant - International World Bodies, Universities, Organisations Etc
27. LISTED AMONG TOPMOST INDIAN PIONEER MEDICINAL PLANTS RESEARCHERS AND THINKERS IN NATIONAL JOURNALS
A.CURRENT-SCIENCE Ayurveda-scientific research and publications, NO-97, VOL-8/25-10-2009.
B.CURRENT SCIENCE -The quest for evidence based Ayurveda: lessons learned, VOL. 102, NO. 10, 25 MAY 2012.
C.J-AIM - A Renaissance for Ayurveda, J. Ayurveda. Integr Med. 2010 Jan-Mar; 1(1): 1–2.
28.LISTED AMONG TOPMOST PIONEER INTERNATIONAL RESEARCHERS IN INTERNATIONAL JOURNAL
A.CELEBRATED RESEARCHERS: SERIAL -7, Link natural products digest, vol. 6 issue 2, 2010, pg13.
29.UNITED NATIONS PROJECTS IMPLEMENTED INTERNATIONALLY
A.UNDP/UNIDO- HERBAL MEDICINES (VIETNAM).
B.WHO- BANGLADESH-MEDICINAL FORMULATIONS FOR GOVT OF BANGLADESH.
C.WHO- USA- CONSULTANCIES ALL OVER USA ON PLANT TOXICITY IN HUMAN FOODCHAIN.
30.BOOK RELEASED AT INDIAN PHARMACEUTICAL CONGRESS (IPC-DELHI-2008)-"HIV, Aids & Bioactive Natural Products” at event diamond jubilee celebrations).
31.MEDIA COVERAGE - Risorine release covered on DD news channel, borax plant covered on BBC news, medicinal awards in news, internet etc
As Hollywood's Biggest Night looms, the nights of Red Carpet interviews, ancillary awards shows, glad-handing anyone and everyone who had a part in making the projects that people spent years of their lives dedicated to, just for the recognition of their peers and the world, the daytime Gifting Suites are kind of a way for the movers and shakers to discover some new things they may have never known they need, to make their lives easier during that next project.
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This Gifting Suite event was held on Friday, March 2nd, in the heart of Hollywood, hosted by the Celebrity Connected team.
The King Kong of suites, around 50 vendor tables in a massive ballroom, 3 aisles with a dizzying number of new baubles and self care products from beyond the imagination, starting with the most impressive display, was Blush & Whimsy several covered smaller tables overflowing with floral arrangements, with their gifting boxes nestled among the blooms, a blossom wall with foot lighting reminiscent of the KimYe wedding photo presenting, under a glass bell jar, the three lipstick tubes being gifted. 10/10 on presentation. Each lipstick has a tiny flower inside, they're also translucent, and they change color based on your skin temperature and pH. *mindblown.gif*
The coolest thing there was the ZUS Smart Car Charger from Nonda in a limited edition gold version. What makes the ZUS special is its the Nest digital thermostat for your car... a simple plug-in that you link to an app for iOS or Android, and it makes it so you can find your car easier when parking, lets you share your parking spot with friends via the app, tracks your mileage, gives you a report on your car's battery health, parking meter alert, dual position USB port so however you plug in, it'll always be right. *USB Superposition.gif* Oh, and it will double the charging speed for your phone. when plugged in... a quick glance at their website Nonda.co they've got everything you'd need to upgrade your car like a cyborg... back up camera, tire pressure sensor, and more... they have the technology and its well under Steve Austin's $6 Million Dollar price tag...
What looked like the most fun was You've Got Crabs a stepped-up version of Go Fish, with an expansion pack that involves shaming one of your friends and they, have to play the remainder of the game wearing rubber crab claws. Designed by the same people who made "Exploding Kittens" featuring art by The Oatmeal I'm not doing the rules or anything about it really much justice, but it looks like it will be a great party game.
There were so many products on display from a Shea Butter sculpture of the Burj Khalifa, to a copper hair mask, chocolate scented perfume, the best apple juice I've ever had, cans of flavored workout water, several chocolatiers, a bespoke pet bed designer from Australia, cold brew coffee, kids clothes that would make Pharrell jealous, contoured pillows, Scandinavian sex toys and a strawberry & habanero pepper jelly to a Las Vegas-based cookie baker who feeds the homeless. But, no gifting suite would be complete without Cyndie Wade and her hand painted wine glasses honoring the nominees.
One last thing... there were two booths, which, Celebrity Connected always seems to have a medicinal cannabis booth or two each event, sadly UPS never delivered either booth's product before the gift suite, so they were reliant on the few samples they had with them, both focused on CBD the non-psychoactive part of marijuana, CBD is the pain reliever and has a myriad of medicinal uses as salves, sprays, and smokeables to help with any number of health issues. Infinite CBD out of Colorado has topicals, vegan gummies, capsules, soap, and specialty CBD delivery systems they call "Rocket Ships" to deal with cramps, and more. The other vendor was S&J Natural Products now, I couldn't quite understand what the gentleman from S&J was saying about bioavailability and Acuity Blends with adaptogenic herbs or microencapsulation or who sizes chained triglycerides. I did try their Oracle Mist with over 75 bioactive terpenes, I'm not sure if it's meant to be a facial spray or some kind of CBD Binaca... but I do not recommend spraying it in your mouth, its fine initially, but I guess as the terpenes bioactivated, it overloaded my tastebuds...
I'm going to recommend InfiniteCBD over S&J's three dollar words and snake oil tactics, as I'm writing this, I'm on their site the products cost more, for less quantity and what I do know about Terpenes is, they're really just the oils that give the cannabis its aroma. If you're adverse to opioids for pain relief and management, CBD in its many delivery methods is certainly worth checking out, because it is not the part of marijuana that gets you High, CBD products are perfectly legal and available to ship around the United States.
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DR. I. C. CHOPRA AWARD, 2000- (FOR SIGNIFICANT WORK IN DRUG DEVELOPMENT) - To commemorate 50th CSIR foundation day, a function was held at PUSA institute Delhi,where the first Dr. I. C. Chopra award was given to Dr. Atal by Union minister for human resources,for noteworthy path breaking achievements in drug development and the field of plant based drugs (particularly the development of a natural non-steroidal drug "Sallaki, and other work on bioenhancers (Piperine), plant based immunomodulators, Vasicine, and Hepatoprotective agents/formulations. Internet sites noted below- www.herbalnet.org/events.htm
PERSONAL AND INSTITUTIONAL AWARDS (For Work done at RRL, Jammu)
(RRL INSTITUTIONAL AWARDS ARE ON WORK DONE BY DR. ATAL AS DIRECTOR AND HEAD OF SCIENTIFIC TEAM) pioneering discoveries in health , nutrition, drugs- allopathic medicine, drug research, drug discoveries, drug development, various plant sciences including medicinal plants, Pharmacognosy, integrated medicine , herbal medicines, Ayurvedic medicines, alternate systems of medicine, Philately, rural development , United Nations grants for rural work / health/ nutrition (pisciculture, food technologhy, etc) , Ethnopharmacology,Essential oils awards(also used in healthcare, eg menthol) , import substitution, best research papers, distinguished teacher award, honors by Medical associations, medical college etc.
1.PROFESSOR BISHAMBAR DAS MEMORIAL AWARD, 1946 - Government College Lahore, award for best plant collection.
2.J.N.TATA ENDOWMENT FELLOWSHIP AWARD, 1954 - for higher studies in USA, at University of Connecticut, Storrs, USA.
3.EOAI BEST PAPER AWARD, 1976 - awarded to Sobti, S.N., Pushpangadan, P., and Atal, C.K. – for paper titled “Genus Ocimum - potential source of new essential oils”, paper presented at the seminar on “Recent developments in the field of essential oils with special reference to Agricultural, chemical, technological, economic and import/export aspects of essential oils”, organized by Essential Oil Association of India (E.O.A.I) on 20-21March, 1976.
4.EOAI BEST PAPER AWARD, 1979 (DHINGRA MEMORIAL MEDAL), - (Essential Oil Association of India) - “A search for new aroma chemicals, structural modifications of Citrionellal”. Indian perfumer, 23(1), 1979, 8-13. Sethi, V.K, Dhar, K.L., Atal, C.K., and Thappa, R.K.
5.GOLD MEDALS TO RRL, JAMMU, YEARS 1970, 1971, 1982 - at Industrial exhibitions held at Jammu/ Srinagar. (See below).
6.SILVER MEDALS TO RRL, JAMMU, YEARS, 1969, 1970 1973 - at Industrial exhibitions held at Jammu/ Srinagar. (Dr. Atal was in the institute from 1964 onwards as Asst. Director, Deputy Director, and finally as Director from 1971 onwards).
7.FICCI AWARD FOR RURAL DEVELOPMENT TO RRL JAMMU, 1980 – (Federation of Indian Chamber of Commerce & Industries award for work done under Dr. Atal). It was presented by the honorable President of India Shri Neelam Sanjiva Reddy at a formal function on April 25, 1981. The citation of the award is as follows – “RRL Jammu has made significant contributions to the economic and social development of the region, introduction of new varieties of fish and fishery technology, new crops, improved storage facilities for grains, solar dryer for fruits and vegetables, utilization of forest and agricultural waste and setting up local resource based rural industries is pioneering. To improve rural health, the laboratory has developed formulation for the control of health. Its efforts at supplementing rural incomes merit recognition.” www.flickr.com/photos/13059662@N06/5782556024/
8.UNITED NATIONS RURAL DEVELOPMENT GRANT TO RRL, 1981-82- in recognition of rural development activities of RRL, Jammu, award of grant worth Rupees 8.5 lacs (period 1981-82) was given to RRL, Jammu by UNICEF, for development of rural Aquaculture of Jammu & Kashmir and educating the rural people(UNICEF rural aquaculture training courses at RRL). www.flickr.com/photos/13059662@N06/6970203227/in/photostr...
9.PROFESSOR G. P. SRIVASTAVA MEMORIAL AWARD (APTI AWARD-1980) Distinguished Teacher Award for Revolutionizing Pharmacognosy in India– (Association of Pharmaceutical Teachers of India).The award function was held on 25th January, 1981 at Nagpur, on occasion of Annual Pharmaceutical congress Convocation, (Jan 23 -25, 1981). Dr. Atal has been the first recipient of the award. The award citation at the function is as follows- “We on behalf of all office bearers and members of the association of Pharmaceutical teachers of India take great pleasure and pride in presenting to you this Professor G. P. Srivastava Memorial award in recognition of your distinguished contributions in the field of Pharmaceutical profession. You helped in revolutionizing the concept of Pharmacognosy as a subject and gave a fruitful new direction to its teaching and research in India. Your contributions as a teacher, researcher and as director of Regional Research Laboratory (CSIR), Jammu have been notably worthy to the profession and have highlighted the all round shining facets of your personality. Your additions to the scientific literature and drug and process developments speak voluminously of your attainments and your services in innumerable but important advising and coordinating capacities to the profession shall ever be remembered.” reference -RRL Newsletter, volume 8, February 1981, no .1. www.flickr.com/photos/13059662@N06/5782556050/
10.HONORARY PROFESSORSHIP, 1980- awarded by the Dept of Chemistry, Jammu University, Jammu & Kashmir. He has also been recognized as a PhD guide by the University of Jammu, Kashmir University, Punjab University and Jiwajee University.
11.ORATION SPEAKER, 1980-(UIPS, PUNJAB UNIVERSITY, CHANDIGARH) - event held at Punjab University Pharmaceutical Sciences department, Chandigarh. www.flickr.com/photos/13059662@N06/6519140107/in/photostr...
12.IMPORT SUBSTITUTION AWARD TO RRL, JAMMU – 1982( Andhra Science & Technology Association)–second prize was awarded to RRL, Jammu at the import substitution competition held in January 1982, on occasion of 42nd All India Industrial Exhibition, Hyderabad, Andhra Pradesh. This was awarded for the development of process for production of Gibberellic acid by submerged fermentation. The projects on submerged fermentation were initiated by Dr. Atal at RRL in June 1975. Gibberellic acid is used by the agricultural industry for increasing the agricultural produce. This was developed and valued at about one third the cost as compared to market value of imported chemical and resulted in significant savings in import and increase in yield of agricultural produce. The significance of the research is detailed at the link provided. www.flickr.com/photos/13059662@N06/5782130619/
13.ESSENTIAL OIL ASSOCIATION OF INDIA SILVER JUBILEE AWARD AND PLAQUE, 1982 – (for outstanding services to the Association and contributions to Essential oil industry) –He was also President of the association for two terms, i.e. 1976 & 1977 & 1978. Essential oils are a good source of livelihood for the rural / agricultural sector that grows these plants. Essential oils are a also a big source of income for the country and the industries based on essential oils like aroma, perfumery, flavoring, medicinal and many other industries worldwide. www.flickr.com/photos/13059662@N06/5782647841/
14.PHILATELIC AWARD (FOR STAMPS COLLECTION AT JAMPEX 1982, JAMMU)-presented by Honorable Governor of Jammu Kashmir Shri B. K. Nehru, on collection of space related stamps. www.flickr.com/photos/13059662@N06/5782130639/
15.SEVERAL PATENTS – based on research and discoveries in science, several national and international patents have been awarded to RRL for work done by Dr. Atal as Director /research head from 1971 till 1987.He formed a core group of talented researchers and produced significant work. This work was continued further and by the year 2000, there were 111 patents awarded to RRL Jammu, which included the same / similar research work started and guided by Dr. Atal, and also extended research completed/continued on those/similar projects after he had left RRL for United Nations in 1985 on deputation.
16.FELLOW COMFORPTS AWARD, 1995, (FOR DISTINGUISHED WORK ON MINOR FOREST PRODUCTS) –IUFRO NEWS,VOL 26,1997,ISSUE 3,PAGE 14- the prestigious award was given by the Centre of Minor forests products, Dehra Dun, India. Minor forest products and non wood forest products are a great source of earning for tribal and rural people and is a way of providing alternate livelihood to these people without straining the woody (jungles and trees) resources of the country. See author section for UN compilation on the topic non wood forest products(serial no 184-211). www.flickr.com/photos/13059662@N06/5782130651/
17.DR. I. C. CHOPRA AWARD, 2000- (FOR SIGNIFICANT WORK IN DRUG DEVELOPMENT) - To commemorate 50th CSIR foundation day, a function was held at PUSA institute Delhi,where the first Dr. I. C. Chopra award was given to Dr. Atal by Union minister for human resources,for noteworthy path breaking achievements in drug development and the field of plant based drugs (particularly the development of a natural non-steroidal drug "Sallaki, and other work on bioenhancers (Piperine), plant based immunomodulators, Vasicine, and Hepatoprotective agents/formulations. Two sites are noted below- www.herbalnet.org/events.htm www.flickr.com/photos/13059662@N06/5782130657/
18.PROFESSOR PRAN NATH MEHRA MEMORIAL AWARD, 2001, BOTANY AWARD (for outstanding research in plant sciences)- (Punjabi University Patiala, Punjab). The renowned and celebrated Prof. P. N. Mehra was the teacher of Dr. Atal, and distinguished Botanist of India based at Punjab University, Chandigarh. The plaque bears the inscription-“Awarded for his pioneering research and outstanding contributions to the knowledge about Aromatic , medicinal and economic plants involving multidisciplinary approach covering Pharmacognosy , Phytochemistry, Physiology, Genetics, breeding, microbiology and tissue culture with the sole aim of improving drug efficacy and increased field production with particular reference to Withania somnifera, Claviceps purpurea, Rauwolfia, Plantago, Hops mushrooms etc together with quality improvement and increase on yield and perfumery plants”. www.flickr.com/photos/13059662@N06/5782130675/sizes/l/in/...
19.HONOURS BY UIPS , PUNJAB UNIVERSITY AT CHANDIGARH
A.CHIEF GUEST, UIPS, 2005-, (serial no 34) Chief Guest, Diamond jubilee Celebrations, 2005 ALUMINI meet, UIPS, Punjab University, Chandigarh. www.flickr.com/photos/13059662@N06/6505960463/in/photostream
B.HONOUR BY APTI AND UIPS, YEAR 2007 (event held on Diamond jubilee Celebrations of the University and honored for contributions to science and teaching –Shawl and plaque presented on 25th October 2007 at the 12th Annual National Convention (25-27th Oct, 2007) organized by Association of Pharmaceutical teachers of India (APTI) and co hosted by University Institute of Pharmaceutical sciences (UIPS), Punjab University, Chandigarh, India. UIPS and PU had different years for Diamond Jubilee as the various departments were shifted from Lahore to Chandigarh at different times after the partition of India.
C.MEMENTO BY UIPS, 2009- Punjab University celebrated his 60th year of graduation by a memento on 24th Dec, 2009, Chandigarh.
20.INDIAN MEDICAL ASSOCIATION EDB CHIKITSA SEVA RATTAN (RATNA) AWARD,2010 (IMA-EDB), (For Research and Discovery of Bioenhancers , establishment of Bioenhancer Concept and resultant launch of Bioenhanced Antitubercular Drug Risorine–The event held on 8th May 2010 was co-organized by Indian Medical Association East Delhi Branch (IMA-EDB) and East Delhi Physician’s Association(EDPA). The citation is as follows-“Awarded to Prof. Dr C. K. Atal, distinguished scientist of India, for revolutionary discovery of world’s first bioenhancer Piperine, for establishing a new concept of bioavailability enhancers/bioenhancers in science which has resulted in the development and marketing of world’s first bioenhanced anti tubercular formulation”. It was researched and developed by RRL Jammu, released officially by CSIR along with former and current ministers for science and technology, Govt. of India and presented to Mr. Bill Gates (Chairman, Microsoft) by the minister at Delhi. www.flickr.com/photos/13059662@N06/4816530020/
21.EDPA AWARD OF APPRECIATION FOR OUTSTANDING CONTRIBUTIONS IN DRUG DEVELOPMENT AND WORK ON PIPERINE - for discovery of world’s first scientifically validated bioenhancer piperine resulting in scientifically establishing the bioenhancer concept and for initiating bioenhanced antitubercular research project resulting in development of world’s first bioenhanced antitubercular formulation developed by IIIM Jammu (CSIR).Event held at Hotel Lemon tree, on 27 July 2014,during medical conference Midcon 2014,theme “infections update, attended by more than 130 leading Physicians and super specialists of East and adjoining areas of Delhi.
OTHER HONORS, INAUGRATIONS, ACHIEVEMENTS & SPECIAL EVENTS
22.GOVERNING BODY OF CCRAS - FOUNDING MEMBER / SIGNATORY TO MEMORANDUM OF ASSOCIATION AT INCEPTION, - details in “Member of governing bodies, Indian Government (heading).
23.FOUNDER MEMBER OF “HERITAGE KASHMIR” (details in art section) - a cultural heritage organization.
24.INAUGURATION OF ANNUAL CONFERENCE AT MEDICAL COLLEGE, HELD BY INDIAN SOCIETY OF HEMATOLOGY AND BLOOD TRANSFUSION, JAMMU, 1982: Inaugurated the event on Nov 6, 1982 at Govt. Medical College, Jammu. www.flickr.com/photos/13059662@N06/6951840853/in/photostr...
25.INAUGURAL HEAD OF THE CSIR COMPLEX, PALAMPUR, HIMACHAL PRADESH, 1983 (now renamed Institute of Himalayan bioresource technology, IHBT). A formal request was made by Chief Minister, Himachal Pradesh to CSIR in 1982 for establishing a centre for use of natural resources of the state. On 2nd July 1983 the foundation stone of this National lab named as CSIR Complex Palampur was laid by Prof. Nurul Hussain in presence of chief minister of the state, Shri Virbhadra Singh, DG-CSIR Dr. Sidhu, Dr. C. K. Atal and others. He was involved in developing the infrastructure of the institute since inception and established the institute as the first head. www.ihbt.res.in/about.htm www.flickr.com/photos/13059662@N06/5782917510/
26.INAUGRATION OF ESSENTIAL OIL ASSOCIATION OF INDIA OFFICE PREMISES, DELHI, 1986 – event was held on 8th Sept, 1986 at premises located at 301, 4832 / 24, Ansari road, Daryaganj, N. Delhi - 110002, India. www.flickr.com/photos/13059662@N06/5782964006/
27.INAUGRATION OF GIRLS HOSTEL, 2000 (RRL HOSTEL FOR WORKING WOMEN), JAMMU - inaugurated the hostel premises at RRL Jammu in October, 2000. www.flickr.com/photos/13059662@N06/6963609909/in/photostream
28.INAUGURAL KEYNOTE ADRESSES AT NATIONAL / INTERNATIONAL CONFERENCES – (serial no 68 and 69- worldwide lecture tours in countries travelled.
29.INAUGURATED CONFERENCE ON BIOENHANCERS ORGANISED BY INDIAN MEDICAL ASSOCIATION EDB, DELHI (see topic below).
30.GUEST OF HONOR AT THE INDIAN MEDICAL ASSOCIATION SEMINAR (EDB), DELHI,2010 –He was the guest of honor at conference on bioenhancers held on 8th may, 2010 at IMA Bhawan (EDB) Delhi which was co- organized by Indian Medical Association (IMA-EDB) & East Delhi Physician’s association (EDPA). It was attended by about 100 doctors from various specialties from Delhi. He was also awarded the Chikitsa Seva Rattan Award on the occasion of the conference on bioenhancers (serial no 20-awards section). www.flickr.com/photos/13059662@N06/4816585820/
31.ON WORLD TB DAY, 2011 OFICIAL RELEASE OF ANTITUBERCULAR FORMULATION BASED ON DRUG DISCOVERY. EVENT WAS HELD AT ANUSANDHAN BHAWAN DELHI-released by CSIR along with Ministry of Science and Technology, Government of India- tuberculosis drug development project started by Dr. Atal at RRL, Jammu, based on his discovery of bioenhancer Piperine resulted in launching of world’s first Piperine bioenhanced anti tubercular formulation Risorine/Risorine kit developed by CSIR as public private partnership. It was officially released on world Tuberculosis day, 24th March 2011 at Anusandhan Bhawan, Rafi marg, Delhi, India in presence of current and former ministers for science and technology, India (Shri Pawan Bansal and Shri Kapil Sibal resp.), Director General CSIR (Dr. Samir Brahmchari) and others. This was covered in national news by multimedia like newspaper, internet and TV (DD news, English and Hindi, on world TB day). pib.nic.in/newsite/erelease.aspx?relid=71235
32.ANTITUBERCULAR DRUG RISORINE PRESENTED TO MR BILL GATES- (MICROSOFT CHAIRMAN) ON WORLD TB DAY BY MINISTER OF SCIENCE & TECHNOLOGY, DELHI, INDIA- Same day 24 March, 2011 at different venue at Delhi, on event of conference “Maximizing India’s capacity: Creating an ecosystem of innovation and research to address public health concerns”, Risorine was presented to celebrity Mr. Bill Gates (Chairman, Microsoft) by S&T Minister, as a safer and cheaper formulation from India. Review of minister and Mr. Gates is given in link below. csirindia.wordpress.com/2011/03/26/world-tuberculosis-day... www.internationalnewsandviews.com/2011/03/25/indias-cultu...
33.SPECIAL GUEST AT ANNUAL CONVOCATION, PUNJAB ENGINEERING COLLEGE, 1982- Special guest on the occasion on 28th March 1982.
34.SPECIAL GUEST AT THE ANNUAL SCIENCE EXHIBITION, JAMMU, 1983 –the exhibition was inaugurated at Kendriya Vidyalaya (KV-I) School, Jammu, on 25th November, 1983.
35.CHIEF GUEST” AT THE UIPS, DIAMOND JUBILEE CELEBRATIONS, PU ALUMINI MEET, CHANDIGARH, 2005: -Dr. Atal was the chief guest at the ALUMINI gathering 2005 organized by the University Institute of Pharmaceutical Sciences, Punjab University in Chandigarh .It was held as part of the Diamond Jubilee celebration of UIPS. An international symposium was also held on the occasion, “India emerging as a global Pharmaceutical competitor” on 25/26 Feb 2005. Dr. Atal chaired the lecture “Herbal Drugs – Challenges and opportunities for India in Global Competition”. He was also invited as guest of Punjab University on the diamond jubilee celebrations on 1st & 2nd Oct, 2007. (UIPS and PU had different years for celebrating the diamond jubilee). www.flickr.com/photos/13059662@N06/6505960463/
36.RELEASED BOOK ON DIAMOND JUBILEE CELEBRATIONS, IPC, DELHI, 2008 - "HIV, AIDS, AND BIOACTIVE NATURAL PRODUCTS",–Released book on 14th Dec, 2008 authored by Dr Vinod Rangari, Principal & Professor of Pharmacognosy, J. L. Chaturvedi College of Pharmacy, Nagpur, India on occasion of Diamond jubilee ceremony of Indian Pharmaceutical Congress held in Netaji Subhash institute of Technology, Dwarka, Delhi. www.amazon.com/Pharmacognosy-Phytochemistry-Vinod-Dr-Rang... (editorial reviews). studiumpress.in/indetail.asp?id=52
37.SCIENTIFIC BOOK DEDICATED TO DR. ATAL, 2010 (National & International Authors) – “Utilization and management of Medicinal plants”, Daya publishing house, Delhi 35, editor in chief V.K. Gupta, co editors Anil. K. Verma, Sushma Koul. digital.csic.es/bitstream/10261/38257/1/CAPITULOS_DE_LIBR... www.google.co.in/url?sa=t&rct=j&q=Utilisation%20a...
38.SCIENTIFIC BOOK DEDICATED TO DR. ATAL, 2010 (National & International Authors ) – “Medicinal plants, Phytochemistry, Pharmacology and Therapeutics”, Daya publishing house, Delhi 35, editor in chief, V.K. Gupta, editors G.D. Singh, Surjeet Singh, A. Kaul. docs.google.com/viewer?a=v&q=cache:XaumNJ9OtRYJ:unilo...
39.FOREWORDS IN THE ABOVE TWO BOOKS BY INTERNATIONAL EXPERTS Serial no 205-225 in PEER REVIEWS, (reviews by Dr. Palpu Pushpangadan - Padamshree awardee , international UN equator initiative laureate, and Dr. H. Wagner - Professor emeritus,Germany, comments on RRL,Jammu).
40.AWARDED INTERNATIONAL JOINT PATENT- ROYALTY (1979 & 1991 RESP) for research on Debelysin– a urolithiolytic drug based on Dolicos biflora Seeds marketed internationally, especially in Byelorussia, Poland and Ukraine , www.ncbi.nlm.nih.gov/pubmed/6889184, Patent-Gustowski; Wlodzimierz (Warsaw, Pl), Kocor; Marian (Warsaw, Pl), Atal; Chand K. (Rrl Jammu-Tawi, In), Orkiszewska; Alicja (Piastow, Pl), Olszewski; Ryszard (Pruszkow, Pl), Wrocinski; Tadeusz (Poznan, Pl) - United States Patent 4156 721, May 29, 1979.