View allAll Photos Tagged Mutates
Mutated Orange Howler Monkey is considered very rare. This one I photographed in the Cano Negro National Wildlife Refuge in Costa Rica, where local people named her "Blondie".
The Mantled Howler is one of the largest Central American monkeys, males can weigh up to 9.8 kg (22 lb). This primate lives up to an elevation of 2,500 m from southern Mexico to northwestern South America. Adults are black with brown or blonde saddles; infants are silver to golden brown and become increasingly like adult coloration until they are about 12 weeks old.
It is the only Central American monkey that eats large quantities of leaves; it has several adaptations to this folivorous diet. Since leaves are difficult to digest and provide less energy than most foods, the mantled howler spends the majority of each day resting and sleeping. The male mantled howler has an enlarged hyoid bone, a hollow bone near the vocal cords, which amplifies the calls made by the male, and is the reason for the name "howler". Howling allows the monkeys to locate each other without expending energy on moving or risking physical confrontation.
The mantled howler lives in groups that can have over 40 members, although groups are usually smaller. Most mantled howlers of both sexes are evicted from the group they were born in upon reaching sexual maturity, resulting in most adult group members being unrelated. The most dominant male, the alpha male, gets preference for food and resting places, and mates with most of the receptive females. The mantled howler is important to the rainforest ecology as a seed disperser and germinator.
Необычайно яркая столбовидная мутация хавортии полосатой. Белые туберкулы с внешней стороны листа сливаются в широкие линии, есть они и с внутренней в виде точек. Редкая форма, деток пока не образует.
Canon EOS 80D, EF 100-400mm f/4.5-5.6L IS II USM, EF 1.4X III
My FB page sharing more of my works.
www.facebook.com/Samson-So-Photography-132675240247135/?f...
A mutated alien of Ga'unk's species. Part of my alien vignette ^_^
The pincers are all moveable. I gave him a winged serpentine like body, like the original, just larger. A little skinnier then I normally make my stuff, but thats to flow better with the idea. I personally love this head design <3
C&C appreciated folks ^_^
I used to keep track of all the different echinaceas in the gardens, but over the years the tags have disappeared and they have mutated to the point that identification is now impossible.
Mutated from the Jackson's Chameleon, of all things, Deathclaws are the most vicious creatures to be found roaming the wasteland. They can't change color, tough.
I couldn't resist doing the celeb photo thing but Don Letts is a top fella and always approachable who I have admired for a long while, anyone who knows me knows that I love punk (huge thanks to ASBObruv for taking me to see the Damned when I was 11 years old) Don Letts is a top DJ and font of knowledge and firsthand experience of punk from 76 and everything alternative beyond that, check out his documentary Punk Attitude:
www.punk77.co.uk/films.dvds/punkattitude.htm
Also he rocked up in a nice Stussy woodland camo jacket ; )))
Mutate private view was a top night (and a bit messy) good time had by all huge shouts to:
Hutch - Pure Evils says can the unknown artist please come to reception and collect their stencil that was found on the floor ; ))) PINT...BITTER!!! ; )))
Leeks - that rum punch hit the spot (always a pleasure; ))
T-wat - good to see you fella....seriously hang in there and we will have a proper drink next time ; ))
Lord Ant - thanks for your support fella ; ))
Asbobruv - stay calm angry bwoy...the Grime community waaaaaants you!! good luck with the Bowie shoot ..yeah? ; )))
Paulo - Its official: Roots Manuva has got an injunction out on you ; ))
SNUB - hardcore armour all the way bruv!! Big luv ; )))
Jonny - was you dazzled boiy the broight loights baaah???? Fuggin wuckud untut? : )))
Sinna - sorry I was giggling when you said your dog was put down but I thought you were telling a joke ; ))
Don - you have me in fits every time...yes we will work that spot..shouts to your man Reefa top boy!! ; )))
Spencer - vodka and coke all the way fella good to meet you ; ))
DEP - luuuuuurv them freaky colours your making ; ))
Ed, Alex, Guy, Garfield - it all came together in the end..good on ya!! ; ))
If you can get along to One Foot In The Grove over the next couple of weeks you will not be disapointed, check out Romanywg's excellent pics of the big guns: www.flickr.com/photos/romanywg/
The common Cowslip is yellow. The name in Latin is "Primula veris" which in translation is "Firstling of spring". (Swedish name: Gullviva)
I found this brinjal in our local vegetable market. For a moment it reminded me of a
penguin, what do you think.??
Красивый гибрид пигмеи х трункаты, хотя растение совсем еще молодое. К сожалению, пестролистность этого экземпляра оказалась совсем неустойчивой, остается одна надежда - мутантность.
I love how the morning sun...
passes thru and over
plastic and glass...
casting a shadow....
as waves of light...
hit the shore...
of the concrete canvas....
where brushed lines of grey...
get covered by charcoal colored darkness....
yes...it is that time of year....
whether from the east or the west....
random designs await....
for one to place....
an object in light....
In the DUNE universe interplanetary travel is facililitated by the secretive Spacing Guild, whose Navigators (humans mutated by Spice and confined to tanks filed with the melange gas) can "Fold Space" to move thier enourmous ships instantaneously from one place in the galaxy to another.
This MOC is my vision of one of the mighty Heighliner's filled with many smaller ships from various Houses across the Imperium, perhaps even House Atreides on their wat to Arrakis.
Although the design is my own it takes inspiration from the visuals in both the David Lynch movie from 1984 and the 2000 Sci-Fi miniseries.
The Spice Must Flow!
Is feudalism, marketing itself as democracy, the underlying operating system for modern civilization’s social, economic and political systems? This is the hypothesis of those who describe current systems of governance, militarism and global economics as a mutated form of feudalism.
If such assumption were true, it would help to explain why, for over 2,000 years, Western civilizations have perpetuated certain distinct characteristics — such as class systems, extreme wealth inequality, power elites, racism, militarism, prison systems and human trafficking.
It would help to explain why the guiding social systems and cultural programing of modern civilizations appear to be rooted in feudalism — focused on the concentration of power and wealth — and appear not to have changed significantly over time. Feudalism has been continuously “repackaged” and “updated” over time, transforming itself into imperialism, colonialism, industrialism and, most recently, into corporate capitalism and globalization.
Over the past few thousand years, human history has been one long story of empire building, predatory colonialism and military conquest. Even now, the majority of people on our planet are either extremely poor or in debt, while the wealthiest few have absolute control over the way those people live.
Our educational systems use standardized tests to sort, rank and classify children, while indoctrinating them with an incomplete understanding of history and manufacturing obedience. Test scores determine society’s winners and losers, and a child’s future social status will depend on their willingness to follow orders and do as instructed.
Our political systems are set up by those with the greatest wealth, allowing powerful individuals and corporations to make laws and wage wars, occupying offices far away from most “common people”, and ruling over the rest of us.
Our modern military campaigns sent young men off like pawns on chess boards to kill people in faraway countries that have resources our corporations want to control. Expensive weapons systems cost trillions of dollars, while back home there is little money left for the education or health care of our “peasant” classes.
Our prison systems are set up so as to see that poor people who violate laws are locked up in cages. In the United States, more African Americans are currently incarcerated than were forced into slavery 200 years ago.
All around us, we can see the old feudal systems transformed into modern versions of the same archaic patterns, resulting in the same social problems and dysfunctions.
It’s a system kept in place by propaganda that is fed to the masses by the media and schools, telling us that our world is based on “progress,” that we are more advanced and “developed” than primitive tribal cultures of the past. When in truth the feudal paradigm of civilization — focused on the social dominance of others and the acquisition of wealth by a small power elite — is in many ways barbaric, authoritarian and unsustainable.
Crime, war, racism, slavery, addiction, human trafficking, environmental destruction and extreme poverty are all symptoms of an underlying systemic imbalance, of a world where predatory and feudalist systems of social organization still dominate our lives.
Such criticism and understanding is not new. Jesus saw the evils of this system, and spoke out against it. Buddha refused to participate in his father’s kingdom, walking off and choosing to live in poverty instead. From Lao Tsu to Gandhi to Martin Luther King, there have been a chorus of voices that have spoken out across the ages. Albert Einstein wrote about this problem over 60 years ago, describing how modern political, economic and media systems were perpetuating oligarchy and manipulating democratic systems.
As we moved into the modern industrial age, large peaceful social movements have risen up to challenge the system – from the abolitionists and women suffragettes to the civil rights movement, anti-war protests, ecology movement and Occupy Wall Street. The old feudal ways of doing things has created endless misery, destroying Nature’s fragile ecosystems and leading the human race to ruin.
The time has come for our species to grow wiser, evolve our thinking and change the way we live upon this planet.
C. C.
The novel coronavirus is getting ever more novel.
TLDR; SARS-CoV-2 mutates regularly, and we are seeing location-based virus evolution during the lockdown period. A single mutation could impact the universality of any vaccine, antibody therapy or drug targeting the binding domain. It also creates the possibility of repeat infections, like the seasonal flu. Gain-of-function mutations have already occurred (D614G), and the new variants are more virulent (614G becomes the leading strain in any new region into which it is introduced within a matter of weeks) and may mediate repeat infections. Some mutations are in regions that might impact antibody binding (V367F). Recombination (S943P) can enable multiple fitness-enhancing mutations to assemble within the same strain making it more pathogenic than the distinct original strains.
Prellis Bio pulled together this table of currently known mutations of SARS-CoV-2, and I asked if I could share. Here are some examples from recent pre-print papers (with attendant caveats):
From Los Alamos National Lab analysis in BioRxiv, May 2020 (and news summary):“Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2”
“We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections.
Although the observed diversity among pandemic SARS-CoV-2 sequences is low, its rapid global spread provides the virus with ample opportunity for natural selection to act upon rare but favorable mutations. This is analogous to the case of influenza. If the pandemic fails to wane, this could exacerbate the potential for antigenic drift and the accumulation of immunologically relevant mutations in the population during the year or more it will take to deliver the first vaccine.
• D614G (a G-to-A base change at position 23,403 in the Wuhan reference strain) is increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread. We were concerned that if the D614G mutation can increase transmissibility, it might also impact severity of disease. Patients carrying the G614 mutation had higher viral loads… a significant difference was observed.
• S943P (a double base mutation: AGT (S) -> CCT (P)) is located in the fusion core region, and is of particular interest as it is spreading via recombination. Recombination requires simultaneous infection of the same host with different viruses, and the two parental strains have to be distinctive enough to manifest in a detectable way in the recombined sequence. Both criteria were met in Belgium."
From BioRxiv India, May 2020, on that same D614G mutation with additional distinct biological properties: "D614G rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare."
From BioRxiv, April 2020: “Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein”
"Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the critical determinant of viral tropism and infectivity. Three mutant types displayed higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective precautions are implemented."
From the Journal of Translational Medicine, April 2020: “Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase (RdRp) variant”
“SARS-CoV-2 is an RNA coronavirus responsible for the pandemic of COVID-19. RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance.
Methods: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020.
Results: We characterized 8 novel recurrent mutations of SARS-CoV-2. America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp, changing its amino acid composition, emerged on February 20th, 2020 in Italy (Lombardy). The SARS-CoV-2 RdRp (also named nsp12) is a key component of the replication/transcription machinery. RdRps are considered among primary targets for antiviral drug development, against a wide variety of viruses [e.g., Remdesivir]. Naturally occurring mutations can lead to drug resistance phenomena, with a significant loss in the binding affinity of these molecules to the RdRp.
Conclusions: These findings suggest that the virus is evolving, and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. It is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.”
Mutated face cow vs. Human skull sheep.
Sony A300, Tamron 90mm2.8
Added to the Macro Mondays "Unusual Combinations" theme.
This was an older shot I thought was fitting for the theme "Unusual Combinations"
Deep down the lowest levels of the Capital City Planet of the federation a rogue professor and his accidentally mutated assistant have hired a small cellar block where they have been brewing a superhuman race and by these labgrown men take over the known observable universe and beyond…
- (Nurse Lizzie) ah Doc finally our superior breed of superhuman species are ready to get their brains…
- (Doc. Incensestone) …yes my Dear Lizzy, we shall finally rule the world, but what a bummer, we got the right DNA for their physique by running that fake fertilization clinic, I mean sadly no, rocket surgery geniuses snapped at out bait of 50 Kredits and a cup of coffee…
- (Nurse) …yeah actually all of our “costumers” were kind of that gang of Hypermasculinized gang of “cavemen” hanging around at the party planet, yes their brain capacity is more similar to a clam than a primate… but hey did they have anabolic muscles all over, oh I am salivation all ready doc.
- (Doc.) Hey! Lizzie darling control primitive urges, we are scientists not lusting savages, save your primeval part of your mind for our bedtime at 22.15 a clock
- (Nurse) Oh Sorry Doc. I must stay strong, let my mind dominate the body and not be governed by simple human nature!
- (Doc.) Now when I got these two specimens at the black market, we can dissolve their organic brain, put them in this test tube and inject it into our new brood of superhumans, our lovely sons!!! oh why did I have to say that out loud? We both know or plan!!!
- (Nurse) Well Darling, all great men talk out loud, I find that hot…
- (S.now-bot) Sir & Madam! I have dissolved their organic brains, but I think we have made a mistake. We only have two dissolved brain specimens, but we have three receiving bodies…
- (Doc.) Silly Droid have you ever heard about the mathematical term of division, split the two dissolved brains in twain, then inject every body with half a brain… this will by far exceed their original “cavemen” brains anyhow!
- (S.now-bot) Yea master! You are the smartest here, I am just a droid…I am your faithful servant!!! Ok Sir, the injection process is ready! Shall I unrestrain the specimens?
- (Doc.) yes ofcause stupid bearing-wingnut-head!!!
The four overgrown he-men are activated and their eyes get a sense of presence they didn’t possess before!
- (Doc.) I am Your father Professor Incensestone! This is my wife and your mother Nurse Lizzie! You my children are superior to other humankind, you are a new breed of superhumans, you are part of our master scheme of supremacy!!! Welcome to our world my children!
- (Jack 1) Hello Daddy nice to see you! I am hungry, time for dinner, mummy bitty! Bitty please!
- (Jack 2) Father, mother, you don’t understand me, I want to listen to rebellious noise bands like: Xome, Driller Killer and T-stallion! They understand me, you are just old and stuck in your ways!!!
- (Jack 3) Father, Mother! So happy to see you! I love you, but I have to warn you, I am a sadly depressed lemming, I need loads of attention and love, I am a delicate soul, contemplating the unthinkable every second, please parents love me, care about me…
- (Jack Cop) Oh how fab to be alive, yes call me camp but I am proud, I am here and I am que…
More was not said by their children because by now, now Doc. Had reached the emergency termination button! The four bodies fell lifeless to the floor!!!
- (Nurse) You killed our children! You monster!!!
- (Doc.) but darling they were faulty, and hey darling they are not our biological children anyway…
- (Nurse) But they were our children! They were dependent on us… I wanted to watch them grow and progress…
By now the Professor made a couple of sign language gestures to his robot servant!
The Robot snook behind the hysterical nurse and injected her with brain dissolvent…
…the poor victim got paralyzed at first then slowly faded away while hearing her husband and professor profess until she ceased to be…
- (Doc.) I am sorry Darling! I didn’t want a family, I thought this was understood when we married, it was always for power, for world domination, again Darling you let your emotions rule… I can’t let you jeopardize our, eh my project, but don’t worry love, your dissolved brain will not be wasted, I will save it for future injection into the next brood of superhumans… Bye Darling! I am sorry it had to end this way! Don’t take it personal, it is all about power!
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The Castel dell'Ovo (castrum Ovi, in Latin), is the oldest castle in the city of Naples [1] and is one of the elements that stand out most in the famous view of the gulf. It is located between the districts of St. Ferdinand and Chiaia, opposite the area of Mergellina.
Because of different events which partially destroyed the original appearance Norman and through eventual reconstruction work that took place during the Angevin and Aragonese, the architectural line of the castle changed dramatically until reaching the stage where it is today.
Its name comes from an ancient legend that the Roman poet Virgil - that in the Middle Ages was considered a magician - buried in the dungeons of the building an egg that kept standing the whole fortress. Its failure would have caused not only the collapse of the castle, but also a series of ruinous disaster to the city of Naples.
During the fourteenth century, at the time of Joanna I, the castle suffered extensive damage due to the partial collapse of the arch on which is resting and, to avoid among the population from spreading panic about allegations future disasters that have hit the city , the queen had sworn he replaced the egg. [2]
The castle rises on tufa Megaride (greek: Megaris), natural offshoot of Mount Echia, which was joined to the mainland by a narrow isthmus of rock. This is the place where it was founded in the eighth century BC Parthenope, hands Cumana.
In the first century BC Lucius Licinius Lucullus acquired in the bottom of a very large (according to some theories that went from Pizzofalcone to Pozzuoli) on the island and built a splendid villa, Villa Licinius Lucullus, which was equipped with a rich library of farms and morays peach trees imported from Persia, which at the time were new along with the cherry trees that the general had brought from Cerasunto. [3] The memory of this property endured in the name of Castrum Lucullanum that the site held until late Roman age . [4]
In the darkest periods for the Empire - half of the fifth century - the villa was fortified by Valentinian III and touched the fate of hosting the deposed last emperor of Rome, Romulus Augustus in 476. [5]
Later the death of Romulus Augustus, on the islet of Megaride and on Mount Echia, already in the late fifth century, settled by Byzantine monks called Pannonia by a matron Barbara with relics of Abbot Severino. Allocated initially in scattered cells (called "hermitages Basilian"), the monks adopted in the seventh century, the Benedictine rule and created a major scriptorium (having probably also what was left of the culinary library).
The monastery, however, was destroyed at the beginning of the tenth century by the Dukes of Naples, to ensure that there will fortify the Saracens using it as a base for the invasion of the city, while the monks retired to Pizzofalcone. In 872, at the time called on the islet of San Salvatore Saracens imprison Bishop Athanasius of Naples, but the joint effort of the fleets of the Duchy of Naples and of the Amalfi Republic frees the bishop and drive out the Muslims [6]. In a document of 1128 in the site it is again cited a fortification called Arx Sancti Saviour from the church of San Pietro which had built the monks. Witness of the settlement of Basilian monks is precisely what remains of this church, founded by the monks themselves and whose earliest records date back to 1324. The only architectural feature prominent left is the entrance preceded by the great arches of the loggia.
Roger the Norman, conquered Naples in 1140, made of Castel dell'Ovo its headquarters. The residential castle however was being used only on a few occasions since, with the completion of Castel Capuano, were moved there all lines of development and trade ground. With the Normans, he began a systematic program of fortification of the site, which was in its first tower Normandy stronghold, and it was the one where the flags were waving.
With the passage of the kingdom to the Swabians by Constance de Hauteville, Castel dell'Ovo it is further strengthened in 1222 by Frederick II, making it the seat of the royal treasury and he built other towers - Tower of Colleville, tower and tower Maestra Middle . In those years, the castle became a royal palace and state prison.
King Charles I of Anjou moved to Castel Nuovo (Maschio Angioino) court. However, he maintained at Castel dell'Ovo - which at this time is beginning to be called Chateau de l'Oeuf or castrum Ovi enchanted - the assets in place to guard better fortified: it did then the residence of the family, by bringing order and many restorations changes, and he kept the royal treasury. In this period, as state prison, he was imprisoned in the castle Conradin before being decapitated in the market square, and the sons of Manfredi and Queen Elena Ducas.
After an earthquake in 1370 that had brought down the natural arch that was the isthmus, Queen Joanna had it rebuilt in brick, even restoring the buildings Norman. After having lived in the castle as a sovereign, the queen was imprisoned here dall'infedele nephew Charles of Durazzo, before ending up in exile in Lucan.
Basilian hermitage
Alfonso V of Aragon, initiator of the Aragonese domination in Naples (1442 - 1503), brought to the castle further restructuring, enriching the royal palace, restoring the pier, enhancing the defensive structures and lowering the towers.
Successogli throne to his son Ferrante, received looting by French troops, to regain the castle he had to bombard with artillery.
Torre Norman
The castle was further damaged by Louis XII of France and Spain's Gonzalo Fernandez de Cordoba, who ousted behalf of Ferdinand II of Aragon, king of Spain, the last Aragonese king of Naples. In 1503 the siege of Ferdinand the Catholic finally demolished what was left of the towers. The castle was then again and massively renovated, taking the form we see today. Mutated weapons systems - from missile weapons and cast the bombs - were rebuilt the octagonal towers, thick walls, and the defensive structures were oriented toward the earth, and no longer to the sea. Defeated the French twice, in Cerignola and Garigliano, there was the complete conquest of the entire Kingdom of Naples in favor of Spain.
During the reign of the Spanish viceroys and then of the Bourbons, the castle was fortified even more with batteries and two drawbridges. The structure completely lost the function of royal residence and from the eighteenth century, even the title of "real factory", and was used as a military outpost and provision - from which the Spaniards bombed the city during the riots of Masaniello - and to prison, where he was imprisoned among others the philosopher Tommaso Campanella before being sentenced to death, and later some Jacobins, Carbonari and liberals such as Carlo Poerio, Luigi Settembrini, Francesco de Sanctis.
View from the sea
Another view of the castle
During the period of the so-called "cleansing", which changed the face of Naples after the Unification of Italy, a project developed by the scientists of writers and artists in 1871 provided for the slaughter of the castle to make way for a new ward. However the project was never implemented and the building remained in the possession of the state property and practically abandoned, until the beginning of the restoration in 1975.
Today is adjacent to the historic district of Saint Lucia and can be visited. In large rooms are held exhibitions, conferences and events. At its base lies the marina of the "Borgo Marinari", with its restaurants and bars, the historical site of some of the most prestigious yacht clubs in Naples.
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)
_-----------------------------------------
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)
——————————————————————————
(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.
Who official website UN .org www.gavi.org/ispe.org
Wikipedia, "The Lancet", "English Journal of Medicine", "Nature", "Science", "Journal of the American Medical Association", etc.
Learning from history: do not flatten the curve of antiviral research!
T Bobrowski, CC Melo-Filho, D Korn, VM Alves...-Drug discovery today, 2020-
A critical overview of computational approaches employed for COVID-19 drug discovery
EN Muratov, R Amaro, CH Andrade, N Brown...-Chemical Society..., 2021-pubs.rsc.org
Global Research Performance on COVID 19 in Dimensions Database
J Balasubramani, M Anbalagan-2021-researchgate.net
Adoption of a contact tracing app for containing COVID-19: a health belief model approach
M Walrave, C Waeterloos...- JMIR public health and..., 2020-publichealth.jmir.org
Prophylactic Treatment Protocol Against the Severity of COVID-19 Using Melatonin
N Charaa, M Chahed, H Ghedira...-Available at SSRN..., 2020-papers.ssrn.com
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet
Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany, New England Journal of Medicine
The actions of respiratory therapists facing COVID-19
Zhu Jiacheng-Respiratory Therapy, 2021-pesquisa.bvsalud.org
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, The Lancet
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China, JAMA, February 7
Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China, JAMA
Delta variant triggers new phase in the pandemic | Science
science.sciencemag.org›
COVID vaccines slash viral spread – but Delta is an unknown
www.nature.com ›articles
Novel coronavirus pneumonia during ophthalmic surgery management strategy and recommendations
YH HUANG, SS LI, X YAO, YR YANG, DH QIN…-jnewmed.com
Delta variant: What is happening with transmission, hospital ...
Risk of long QT syndrome in novel coronavirus COVID-19
VN Oslopov, JV Oslopova, EV Hazova…-Kazan medical…, 2020-kazanmedjournal.ru
Study compares mRNA and adenovirus-based SARS-CoV-2 vaccines ...
First molecular-based detection of SARS-CoV-2 virus in the field-collected houseflies
A Soltani, M Jamalidoust, A Hosseinpour, M Vahedi...-Scientific Reports, 2021-nature.com
Covid 19 DELTA Variant Archives-Online essay writing service
sourceessay.com ›tag› covid-19-delta-variant
SARS-CoV-2 Delta variant Likely to become dominant in the ...
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
Nikon D3200 - 90mm f/2.8 Macro -
This red peace lily stamen is clearly mutated and struck me as beautiful.
go large:
www.flickr.com/photos/asboluv/3971445934/sizes/o/
8ft x 4ft board for Mutate Britain show One Foot In The Grove - London..
Ladbroke Grove, Under The Westway, 3 - 6 Acklam Road, London W10 5YU.
thanks to Hutch for picture as my camera was f*@#*d
; ))
MuTATE Britain 2009, under the westway, Ladbroke Grove, London. The show runs until the 25th of October
photos courtesy of romanywg
Africa on the Square Trafalgar Square London Oct 15 2016 Kasai Masai with Nickens Nkoso Congo Band from DRC and Diamond Mutate from the Cameroon
Mutate Britain - One Foot In The Grove
Ladbroke Grove, Under The Westway, 3 - 6 Acklam Road, London W10 5YU.
9th Oct - 1st Nov. 2009.
Pre-Launch party, Fri 2nd - Sun 4th Oct. 3pm till late.
Our town has a pretty mild micro-climate anyway, but this is ridiculous. I shot this photo on November 13, 2019. This hydrangea plant seems to reside in a nano-climate* of its own. We had already had some nights with temperatures below freezing, according to the local weather report.
As shown at the bottom of the photo, this plant is unprotected and right next to the asphalt sidewalk. It is on the shady side of an ordinary street; actually in the higher-elevation (more windy) part of town. I wish I had shot its lone bloom ca. 5 days earlier because it was even pinker then.
* Or maybe there is no nano-climate. Perhaps this is just some kind of accidentally hardy, mutated hydrangea.
NB - Shot with my ancient iPhone 4S, then cropped and edited on my computer.
Location: Riehen BS Switzerland.
In my album: Dan's Flower Power.
After all the things I've seen the past couple days, it's sorta weird that this surprises me. Dionaea had the choice of either surrendering to us or death. And he chose death. A painful, fiery death. All I heard was him falling into the molten metal. There was no screams, no begging for help, nothing. He just silently burned to death and sunk into the vat. Like he accepted his fate. I had enough for the night. Even then before I could leave there was something I saw just outside the steel mill that I had to deal with Something I think I actually saw a couple times during this whole case.
"Tim? What are you doing? We gotta go, the police are gonna--what the hell is that?!"
"Something Otto left us to remember him by."
"Yeah, but what? My God, is it glowing?"
"I saw it a couple times before across other places Dionaea's been but I never had a chance to look up close. These are spores."
"Spores? Oh my god, get away from it then!!"
"It's not dangerous. Not yet, anyway. I took a sample, but I think I know what it is. This might be the same kind of spore that mutated Otto into....well, Dionaea."
"So....there's gonna be more of him?"
"Maybe. If we work quick we can make a cure easily. But who knows how many of these spores he left behind. You got any thermite on you?"
"Yeah...why?"
"Give it here."
Steph takes the thermite in her belt and hands it to me. I take it and drop it on the spore, lighting it. As it burns it makes this creepy hissing nose. We stand there and watch the fire take it like we just watched the fire take Dionaea. Even in death he's still a threat. That's why we're here, though....
Check out my web site : www.ortbaldauf.com
and my www.500px.com/ortbaldauf site..
© Photo is the property of Ort Baldauf. Do not use this photo on or off the web without my written permission. Thank you