“We have been unwitting participants in a global gut remodeling experiment over past 100 years.” — Prof Bruce German, UC Davis

 

David Kyle, Evolve BioSystems at SynBioBeta 2018

• 80% of immune system associated with gut. The gut is the nursery for immune system

• Huge growth in immune disorders in children: Asthma 4x, Allergy 4x, Diabetes 5x

• Breast milk: 15% of its energy not usable by baby – it feeds the microflora in the gut.

• Baby Bif is missing in western babies. Instead, we see opportunistic pathogens, leading to a different pH of stools (5 vs 6 bad). The ph has shifted over 100 years.

The Roman Baths are well-preserved thermae in the city of Bath, Somerset, England. A temple was constructed on the site between 60 and 70 AD in the first few decades of Roman Britain. Its presence led to the development of the small Roman urban settlement known as Aquae Sulis around the site. The Roman baths—designed for public bathing—were used until the end of Roman rule in Britain in the 5th century AD. According to the Anglo-Saxon Chronicle, the original Roman baths were in ruins a century later. The area around the natural springs was redeveloped several times during the Early and Late Middle Ages.

 

The Roman Baths are preserved in four main features: the Sacred Spring, the Roman Temple, the Roman Bath House, and a museum which holds artefacts from Aquae Sulis. However, all buildings at street level date from the 19th century. It is a major tourist attraction in the UK, and together with the Grand Pump Room, receives more than 1.3 million visitors annually. Visitors can tour the baths and museum but cannot enter the water.

 

Hot spring

The water is sourced from rainfall on the nearby Mendip Hills, which then percolates down through limestone aquifers to a depth of between 2,700 and 4,300 metres (8,900 and 14,100 ft). Geothermal energy raises the water temperature here to between 69 and 96 °C (156.2 and 204.8 °F). Under pressure, the heated water rises along fissures and faults in the limestone, until it bubbles up from the ground into the baths. This process is similar to an enhanced geothermal system, which also makes use of the high pressures and temperatures below the Earth's crust. Hot water at a temperature of 46 °C (114.8 °F) rises here at the rate of 1,170,000 litres (257,364 imp gal) every day, from a geological fault (the Pennyquick fault). In 1982 a new spa water bore-hole was sunk, providing a clean and safe supply of spa water for drinking in the Pump Room.

 

Water quality

Bath was charged with responsibility for the hot springs in a Royal Charter of 1591 granted by Elizabeth I. This duty has now passed to Bath and North East Somerset Council, who monitor pressure, temperature and flow rates. The thermal waters contain sodium, calcium, chloride and sulphate ions in high concentrations.

 

The Roman Baths are no longer used for bathing. In October 1978, a young girl swimming in the restored Roman Bath with the Bath Dolphins, a local swimming club, contracted naegleriasis and died, leading to the closure of the bath for several years. Tests showed Naegleria fowleri, a deadly pathogen, in the water. The newly constructed Thermae Bath Spa nearby, and the refurbished Cross Bath, allow modern-day bathers to experience the waters via a series of more recently drilled boreholes.

 

Roman Britain was the territory that became the Roman province of Britannia after the Roman conquest of Britain, consisting of a large part of the island of Great Britain. The occupation lasted from AD 43 to AD 410.

 

Julius Caesar invaded Britain in 55 and 54 BC as part of his Gallic Wars. According to Caesar, the Britons had been overrun or culturally assimilated by the Belgae during the British Iron Age and had been aiding Caesar's enemies. The Belgae were the only Celtic tribe to cross the sea into Britain, for to all other Celtic tribes this land was unknown. He received tribute, installed the friendly king Mandubracius over the Trinovantes, and returned to Gaul. Planned invasions under Augustus were called off in 34, 27, and 25 BC. In 40 AD, Caligula assembled 200,000 men at the Channel on the continent, only to have them gather seashells (musculi) according to Suetonius, perhaps as a symbolic gesture to proclaim Caligula's victory over the sea. Three years later, Claudius directed four legions to invade Britain and restore the exiled king Verica over the Atrebates. The Romans defeated the Catuvellauni, and then organized their conquests as the province of Britain. By 47 AD, the Romans held the lands southeast of the Fosse Way. Control over Wales was delayed by reverses and the effects of Boudica's uprising, but the Romans expanded steadily northward.

 

The conquest of Britain continued under command of Gnaeus Julius Agricola (77–84), who expanded the Roman Empire as far as Caledonia. In mid-84 AD, Agricola faced the armies of the Caledonians, led by Calgacus, at the Battle of Mons Graupius. Battle casualties were estimated by Tacitus to be upwards of 10,000 on the Caledonian side and about 360 on the Roman side. The bloodbath at Mons Graupius concluded the forty-year conquest of Britain, a period that possibly saw between 100,000 and 250,000 Britons killed. In the context of pre-industrial warfare and of a total population of Britain of c. 2 million, these are very high figures.

 

Under the 2nd-century emperors Hadrian and Antoninus Pius, two walls were built to defend the Roman province from the Caledonians, whose realms in the Scottish Highlands were never controlled. Around 197 AD, the Severan Reforms divided Britain into two provinces: Britannia Superior and Britannia Inferior. During the Diocletian Reforms, at the end of the 3rd century, Britannia was divided into four provinces under the direction of a vicarius, who administered the Diocese of the Britains. A fifth province, Valentia, is attested in the later 4th century. For much of the later period of the Roman occupation, Britannia was subject to barbarian invasions and often came under the control of imperial usurpers and imperial pretenders. The final Roman withdrawal from Britain occurred around 410; the native kingdoms are considered to have formed Sub-Roman Britain after that.

 

Following the conquest of the Britons, a distinctive Romano-British culture emerged as the Romans introduced improved agriculture, urban planning, industrial production, and architecture. The Roman goddess Britannia became the female personification of Britain. After the initial invasions, Roman historians generally only mention Britain in passing. Thus, most present knowledge derives from archaeological investigations and occasional epigraphic evidence lauding the Britannic achievements of an emperor. Roman citizens settled in Britain from many parts of the Empire.

 

History

Britain was known to the Classical world. The Greeks, the Phoenicians and the Carthaginians traded for Cornish tin in the 4th century BC. The Greeks referred to the Cassiterides, or "tin islands", and placed them near the west coast of Europe. The Carthaginian sailor Himilco is said to have visited the island in the 6th or 5th century BC and the Greek explorer Pytheas in the 4th. It was regarded as a place of mystery, with some writers refusing to believe it existed.

 

The first direct Roman contact was when Julius Caesar undertook two expeditions in 55 and 54 BC, as part of his conquest of Gaul, believing the Britons were helping the Gallic resistance. The first expedition was more a reconnaissance than a full invasion and gained a foothold on the coast of Kent but was unable to advance further because of storm damage to the ships and a lack of cavalry. Despite the military failure, it was a political success, with the Roman Senate declaring a 20-day public holiday in Rome to honour the unprecedented achievement of obtaining hostages from Britain and defeating Belgic tribes on returning to the continent.

 

The second invasion involved a substantially larger force and Caesar coerced or invited many of the native Celtic tribes to pay tribute and give hostages in return for peace. A friendly local king, Mandubracius, was installed, and his rival, Cassivellaunus, was brought to terms. Hostages were taken, but historians disagree over whether any tribute was paid after Caesar returned to Gaul.

 

Caesar conquered no territory and left no troops behind, but he established clients and brought Britain into Rome's sphere of influence. Augustus planned invasions in 34, 27 and 25 BC, but circumstances were never favourable, and the relationship between Britain and Rome settled into one of diplomacy and trade. Strabo, writing late in Augustus's reign, claimed that taxes on trade brought in more annual revenue than any conquest could. Archaeology shows that there was an increase in imported luxury goods in southeastern Britain. Strabo also mentions British kings who sent embassies to Augustus, and Augustus's own Res Gestae refers to two British kings he received as refugees. When some of Tiberius's ships were carried to Britain in a storm during his campaigns in Germany in 16 AD, they came back with tales of monsters.

 

Rome appears to have encouraged a balance of power in southern Britain, supporting two powerful kingdoms: the Catuvellauni, ruled by the descendants of Tasciovanus, and the Atrebates, ruled by the descendants of Commius. This policy was followed until 39 or 40 AD, when Caligula received an exiled member of the Catuvellaunian dynasty and planned an invasion of Britain that collapsed in farcical circumstances before it left Gaul. When Claudius successfully invaded in 43 AD, it was in aid of another fugitive British ruler, Verica of the Atrebates.

 

Roman invasion

The invasion force in 43 AD was led by Aulus Plautius,[26] but it is unclear how many legions were sent. The Legio II Augusta, commanded by future emperor Vespasian, was the only one directly attested to have taken part. The Legio IX Hispana, the XIV Gemina (later styled Martia Victrix) and the XX (later styled Valeria Victrix) are known to have served during the Boudican Revolt of 60/61, and were probably there since the initial invasion. This is not certain because the Roman army was flexible, with units being moved around whenever necessary. The IX Hispana may have been permanently stationed, with records showing it at Eboracum (York) in 71 and on a building inscription there dated 108, before being destroyed in the east of the Empire, possibly during the Bar Kokhba revolt.

 

The invasion was delayed by a troop mutiny until an imperial freedman persuaded them to overcome their fear of crossing the Ocean and campaigning beyond the limits of the known world. They sailed in three divisions, and probably landed at Richborough in Kent; at least part of the force may have landed near Fishbourne, West Sussex.

 

The Catuvellauni and their allies were defeated in two battles: the first, assuming a Richborough landing, on the river Medway, the second on the river Thames. One of their leaders, Togodumnus, was killed, but his brother Caratacus survived to continue resistance elsewhere. Plautius halted at the Thames and sent for Claudius, who arrived with reinforcements, including artillery and elephants, for the final march to the Catuvellaunian capital, Camulodunum (Colchester). Vespasian subdued the southwest, Cogidubnus was set up as a friendly king of several territories, and treaties were made with tribes outside direct Roman control.

 

Establishment of Roman rule

After capturing the south of the island, the Romans turned their attention to what is now Wales. The Silures, Ordovices and Deceangli remained implacably opposed to the invaders and for the first few decades were the focus of Roman military attention, despite occasional minor revolts among Roman allies like the Brigantes and the Iceni. The Silures were led by Caratacus, and he carried out an effective guerrilla campaign against Governor Publius Ostorius Scapula. Finally, in 51, Ostorius lured Caratacus into a set-piece battle and defeated him. The British leader sought refuge among the Brigantes, but their queen, Cartimandua, proved her loyalty by surrendering him to the Romans. He was brought as a captive to Rome, where a dignified speech he made during Claudius's triumph persuaded the emperor to spare his life. The Silures were still not pacified, and Cartimandua's ex-husband Venutius replaced Caratacus as the most prominent leader of British resistance.

 

On Nero's accession, Roman Britain extended as far north as Lindum. Gaius Suetonius Paulinus, the conqueror of Mauretania (modern day Algeria and Morocco), then became governor of Britain, and in 60 and 61 he moved against Mona (Anglesey) to settle accounts with Druidism once and for all. Paulinus led his army across the Menai Strait and massacred the Druids and burnt their sacred groves.

 

While Paulinus was campaigning in Mona, the southeast of Britain rose in revolt under the leadership of Boudica. She was the widow of the recently deceased king of the Iceni, Prasutagus. The Roman historian Tacitus reports that Prasutagus had left a will leaving half his kingdom to Nero in the hope that the remainder would be left untouched. He was wrong. When his will was enforced, Rome[clarification needed] responded by violently seizing the tribe's lands in full. Boudica protested. In consequence, Rome[clarification needed] punished her and her daughters by flogging and rape. In response, the Iceni, joined by the Trinovantes, destroyed the Roman colony at Camulodunum (Colchester) and routed the part of the IXth Legion that was sent to relieve it. Paulinus rode to London (then called Londinium), the rebels' next target, but concluded it could not be defended. Abandoned, it was destroyed, as was Verulamium (St. Albans). Between seventy and eighty thousand people are said to have been killed in the three cities. But Paulinus regrouped with two of the three legions still available to him, chose a battlefield, and, despite being outnumbered by more than twenty to one, defeated the rebels in the Battle of Watling Street. Boudica died not long afterwards, by self-administered poison or by illness. During this time, the Emperor Nero considered withdrawing Roman forces from Britain altogether.

 

There was further turmoil in 69, the "Year of the Four Emperors". As civil war raged in Rome, weak governors were unable to control the legions in Britain, and Venutius of the Brigantes seized his chance. The Romans had previously defended Cartimandua against him, but this time were unable to do so. Cartimandua was evacuated, and Venutius was left in control of the north of the country. After Vespasian secured the empire, his first two appointments as governor, Quintus Petillius Cerialis and Sextus Julius Frontinus, took on the task of subduing the Brigantes and Silures respectively.[38] Frontinus extended Roman rule to all of South Wales, and initiated exploitation of the mineral resources, such as the gold mines at Dolaucothi.

 

In the following years, the Romans conquered more of the island, increasing the size of Roman Britain. Governor Gnaeus Julius Agricola, father-in-law to the historian Tacitus, conquered the Ordovices in 78. With the XX Valeria Victrix legion, Agricola defeated the Caledonians in 84 at the Battle of Mons Graupius, in north-east Scotland. This was the high-water mark of Roman territory in Britain: shortly after his victory, Agricola was recalled from Britain back to Rome, and the Romans initially retired to a more defensible line along the Forth–Clyde isthmus, freeing soldiers badly needed along other frontiers.

 

For much of the history of Roman Britain, a large number of soldiers were garrisoned on the island. This required that the emperor station a trusted senior man as governor of the province. As a result, many future emperors served as governors or legates in this province, including Vespasian, Pertinax, and Gordian I.

 

Roman military organisation in the north

In 84 AD

In 84 AD

 

In 155 AD

In 155 AD

 

Hadrian's Wall, and Antonine Wall

There is no historical source describing the decades that followed Agricola's recall. Even the name of his replacement is unknown. Archaeology has shown that some Roman forts south of the Forth–Clyde isthmus were rebuilt and enlarged; others appear to have been abandoned. By 87 the frontier had been consolidated on the Stanegate. Roman coins and pottery have been found circulating at native settlement sites in the Scottish Lowlands in the years before 100, indicating growing Romanisation. Some of the most important sources for this era are the writing tablets from the fort at Vindolanda in Northumberland, mostly dating to 90–110. These tablets provide evidence for the operation of a Roman fort at the edge of the Roman Empire, where officers' wives maintained polite society while merchants, hauliers and military personnel kept the fort operational and supplied.

 

Around 105 there appears to have been a serious setback at the hands of the tribes of the Picts: several Roman forts were destroyed by fire, with human remains and damaged armour at Trimontium (at modern Newstead, in SE Scotland) indicating hostilities at least at that site.[citation needed] There is also circumstantial evidence that auxiliary reinforcements were sent from Germany, and an unnamed British war of the period is mentioned on the gravestone of a tribune of Cyrene. Trajan's Dacian Wars may have led to troop reductions in the area or even total withdrawal followed by slighting of the forts by the Picts rather than an unrecorded military defeat. The Romans were also in the habit of destroying their own forts during an orderly withdrawal, in order to deny resources to an enemy. In either case, the frontier probably moved south to the line of the Stanegate at the Solway–Tyne isthmus around this time.

 

A new crisis occurred at the beginning of Hadrian's reign): a rising in the north which was suppressed by Quintus Pompeius Falco. When Hadrian reached Britannia on his famous tour of the Roman provinces around 120, he directed an extensive defensive wall, known to posterity as Hadrian's Wall, to be built close to the line of the Stanegate frontier. Hadrian appointed Aulus Platorius Nepos as governor to undertake this work who brought the Legio VI Victrix legion with him from Germania Inferior. This replaced the famous Legio IX Hispana, whose disappearance has been much discussed. Archaeology indicates considerable political instability in Scotland during the first half of the 2nd century, and the shifting frontier at this time should be seen in this context.

 

In the reign of Antoninus Pius (138–161) the Hadrianic border was briefly extended north to the Forth–Clyde isthmus, where the Antonine Wall was built around 142 following the military reoccupation of the Scottish lowlands by a new governor, Quintus Lollius Urbicus.

 

The first Antonine occupation of Scotland ended as a result of a further crisis in 155–157, when the Brigantes revolted. With limited options to despatch reinforcements, the Romans moved their troops south, and this rising was suppressed by Governor Gnaeus Julius Verus. Within a year the Antonine Wall was recaptured, but by 163 or 164 it was abandoned. The second occupation was probably connected with Antoninus's undertakings to protect the Votadini or his pride in enlarging the empire, since the retreat to the Hadrianic frontier occurred not long after his death when a more objective strategic assessment of the benefits of the Antonine Wall could be made. The Romans did not entirely withdraw from Scotland at this time: the large fort at Newstead was maintained along with seven smaller outposts until at least 180.

 

During the twenty-year period following the reversion of the frontier to Hadrian's Wall in 163/4, Rome was concerned with continental issues, primarily problems in the Danubian provinces. Increasing numbers of hoards of buried coins in Britain at this time indicate that peace was not entirely achieved. Sufficient Roman silver has been found in Scotland to suggest more than ordinary trade, and it is likely that the Romans were reinforcing treaty agreements by paying tribute to their implacable enemies, the Picts.

 

In 175, a large force of Sarmatian cavalry, consisting of 5,500 men, arrived in Britannia, probably to reinforce troops fighting unrecorded uprisings. In 180, Hadrian's Wall was breached by the Picts and the commanding officer or governor was killed there in what Cassius Dio described as the most serious war of the reign of Commodus. Ulpius Marcellus was sent as replacement governor and by 184 he had won a new peace, only to be faced with a mutiny from his own troops. Unhappy with Marcellus's strictness, they tried to elect a legate named Priscus as usurper governor; he refused, but Marcellus was lucky to leave the province alive. The Roman army in Britannia continued its insubordination: they sent a delegation of 1,500 to Rome to demand the execution of Tigidius Perennis, a Praetorian prefect who they felt had earlier wronged them by posting lowly equites to legate ranks in Britannia. Commodus met the party outside Rome and agreed to have Perennis killed, but this only made them feel more secure in their mutiny.

 

The future emperor Pertinax (lived 126–193) was sent to Britannia to quell the mutiny and was initially successful in regaining control, but a riot broke out among the troops. Pertinax was attacked and left for dead, and asked to be recalled to Rome, where he briefly succeeded Commodus as emperor in 192.

 

3rd century

The death of Commodus put into motion a series of events which eventually led to civil war. Following the short reign of Pertinax, several rivals for the emperorship emerged, including Septimius Severus and Clodius Albinus. The latter was the new governor of Britannia, and had seemingly won the natives over after their earlier rebellions; he also controlled three legions, making him a potentially significant claimant. His sometime rival Severus promised him the title of Caesar in return for Albinus's support against Pescennius Niger in the east. Once Niger was neutralised, Severus turned on his ally in Britannia; it is likely that Albinus saw he would be the next target and was already preparing for war.

 

Albinus crossed to Gaul in 195, where the provinces were also sympathetic to him, and set up at Lugdunum. Severus arrived in February 196, and the ensuing battle was decisive. Albinus came close to victory, but Severus's reinforcements won the day, and the British governor committed suicide. Severus soon purged Albinus's sympathisers and perhaps confiscated large tracts of land in Britain as punishment. Albinus had demonstrated the major problem posed by Roman Britain. In order to maintain security, the province required the presence of three legions, but command of these forces provided an ideal power base for ambitious rivals. Deploying those legions elsewhere would strip the island of its garrison, leaving the province defenceless against uprisings by the native Celtic tribes and against invasion by the Picts and Scots.

 

The traditional view is that northern Britain descended into anarchy during Albinus's absence. Cassius Dio records that the new Governor, Virius Lupus, was obliged to buy peace from a fractious northern tribe known as the Maeatae. The succession of militarily distinguished governors who were subsequently appointed suggests that enemies of Rome were posing a difficult challenge, and Lucius Alfenus Senecio's report to Rome in 207 describes barbarians "rebelling, over-running the land, taking loot and creating destruction". In order to rebel, of course, one must be a subject – the Maeatae clearly did not consider themselves such. Senecio requested either reinforcements or an Imperial expedition, and Severus chose the latter, despite being 62 years old. Archaeological evidence shows that Senecio had been rebuilding the defences of Hadrian's Wall and the forts beyond it, and Severus's arrival in Britain prompted the enemy tribes to sue for peace immediately. The emperor had not come all that way to leave without a victory, and it is likely that he wished to provide his teenage sons Caracalla and Geta with first-hand experience of controlling a hostile barbarian land.

 

Northern campaigns, 208–211

An invasion of Caledonia led by Severus and probably numbering around 20,000 troops moved north in 208 or 209, crossing the Wall and passing through eastern Scotland on a route similar to that used by Agricola. Harried by punishing guerrilla raids by the northern tribes and slowed by an unforgiving terrain, Severus was unable to meet the Caledonians on a battlefield. The emperor's forces pushed north as far as the River Tay, but little appears to have been achieved by the invasion, as peace treaties were signed with the Caledonians. By 210 Severus had returned to York, and the frontier had once again become Hadrian's Wall. He assumed the title Britannicus but the title meant little with regard to the unconquered north, which clearly remained outside the authority of the Empire. Almost immediately, another northern tribe, the Maeatae, went to war. Caracalla left with a punitive expedition, but by the following year his ailing father had died and he and his brother left the province to press their claim to the throne.

 

As one of his last acts, Severus tried to solve the problem of powerful and rebellious governors in Britain by dividing the province into Britannia Superior and Britannia Inferior. This kept the potential for rebellion in check for almost a century. Historical sources provide little information on the following decades, a period known as the Long Peace. Even so, the number of buried hoards found from this period rises, suggesting continuing unrest. A string of forts were built along the coast of southern Britain to control piracy; and over the following hundred years they increased in number, becoming the Saxon Shore Forts.

 

During the middle of the 3rd century, the Roman Empire was convulsed by barbarian invasions, rebellions and new imperial pretenders. Britannia apparently avoided these troubles, but increasing inflation had its economic effect. In 259 a so-called Gallic Empire was established when Postumus rebelled against Gallienus. Britannia was part of this until 274 when Aurelian reunited the empire.

 

Around the year 280, a half-British officer named Bonosus was in command of the Roman's Rhenish fleet when the Germans managed to burn it at anchor. To avoid punishment, he proclaimed himself emperor at Colonia Agrippina (Cologne) but was crushed by Marcus Aurelius Probus. Soon afterwards, an unnamed governor of one of the British provinces also attempted an uprising. Probus put it down by sending irregular troops of Vandals and Burgundians across the Channel.

 

The Carausian Revolt led to a short-lived Britannic Empire from 286 to 296. Carausius was a Menapian naval commander of the Britannic fleet; he revolted upon learning of a death sentence ordered by the emperor Maximian on charges of having abetted Frankish and Saxon pirates and having embezzled recovered treasure. He consolidated control over all the provinces of Britain and some of northern Gaul while Maximian dealt with other uprisings. An invasion in 288 failed to unseat him and an uneasy peace ensued, with Carausius issuing coins and inviting official recognition. In 293, the junior emperor Constantius Chlorus launched a second offensive, besieging the rebel port of Gesoriacum (Boulogne-sur-Mer) by land and sea. After it fell, Constantius attacked Carausius's other Gallic holdings and Frankish allies and Carausius was usurped by his treasurer, Allectus. Julius Asclepiodotus landed an invasion fleet near Southampton and defeated Allectus in a land battle.

 

Diocletian's reforms

As part of Diocletian's reforms, the provinces of Roman Britain were organized as a diocese governed by a vicarius under a praetorian prefect who, from 318 to 331, was Junius Bassus who was based at Augusta Treverorum (Trier).

 

The vicarius was based at Londinium as the principal city of the diocese. Londinium and Eboracum continued as provincial capitals and the territory was divided up into smaller provinces for administrative efficiency.

 

Civilian and military authority of a province was no longer exercised by one official and the governor was stripped of military command which was handed over to the Dux Britanniarum by 314. The governor of a province assumed more financial duties (the procurators of the Treasury ministry were slowly phased out in the first three decades of the 4th century). The Dux was commander of the troops of the Northern Region, primarily along Hadrian's Wall and his responsibilities included protection of the frontier. He had significant autonomy due in part to the distance from his superiors.

 

The tasks of the vicarius were to control and coordinate the activities of governors; monitor but not interfere with the daily functioning of the Treasury and Crown Estates, which had their own administrative infrastructure; and act as the regional quartermaster-general of the armed forces. In short, as the sole civilian official with superior authority, he had general oversight of the administration, as well as direct control, while not absolute, over governors who were part of the prefecture; the other two fiscal departments were not.

 

The early-4th-century Verona List, the late-4th-century work of Sextus Rufus, and the early-5th-century List of Offices and work of Polemius Silvius all list four provinces by some variation of the names Britannia I, Britannia II, Maxima Caesariensis, and Flavia Caesariensis; all of these seem to have initially been directed by a governor (praeses) of equestrian rank. The 5th-century sources list a fifth province named Valentia and give its governor and Maxima's a consular rank. Ammianus mentions Valentia as well, describing its creation by Count Theodosius in 369 after the quelling of the Great Conspiracy. Ammianus considered it a re-creation of a formerly lost province, leading some to think there had been an earlier fifth province under another name (may be the enigmatic "Vespasiana"), and leading others to place Valentia beyond Hadrian's Wall, in the territory abandoned south of the Antonine Wall.

 

Reconstructions of the provinces and provincial capitals during this period partially rely on ecclesiastical records. On the assumption that the early bishoprics mimicked the imperial hierarchy, scholars use the list of bishops for the 314 Council of Arles. The list is patently corrupt: the British delegation is given as including a Bishop "Eborius" of Eboracum and two bishops "from Londinium" (one de civitate Londinensi and the other de civitate colonia Londinensium). The error is variously emended: Bishop Ussher proposed Colonia, Selden Col. or Colon. Camalodun., and Spelman Colonia Cameloduni (all various names of Colchester); Gale and Bingham offered colonia Lindi and Henry Colonia Lindum (both Lincoln); and Bishop Stillingfleet and Francis Thackeray read it as a scribal error of Civ. Col. Londin. for an original Civ. Col. Leg. II (Caerleon). On the basis of the Verona List, the priest and deacon who accompanied the bishops in some manuscripts are ascribed to the fourth province.

 

In the 12th century, Gerald of Wales described the supposedly metropolitan sees of the early British church established by the legendary SS Fagan and "Duvian". He placed Britannia Prima in Wales and western England with its capital at "Urbs Legionum" (Caerleon); Britannia Secunda in Kent and southern England with its capital at "Dorobernia" (Canterbury); Flavia in Mercia and central England with its capital at "Lundonia" (London); "Maximia" in northern England with its capital at Eboracum (York); and Valentia in "Albania which is now Scotland" with its capital at St Andrews. Modern scholars generally dispute the last: some place Valentia at or beyond Hadrian's Wall but St Andrews is beyond even the Antonine Wall and Gerald seems to have simply been supporting the antiquity of its church for political reasons.

 

A common modern reconstruction places the consular province of Maxima at Londinium, on the basis of its status as the seat of the diocesan vicarius; places Prima in the west according to Gerald's traditional account but moves its capital to Corinium of the Dobunni (Cirencester) on the basis of an artifact recovered there referring to Lucius Septimius, a provincial rector; places Flavia north of Maxima, with its capital placed at Lindum Colonia (Lincoln) to match one emendation of the bishops list from Arles;[d] and places Secunda in the north with its capital at Eboracum (York). Valentia is placed variously in northern Wales around Deva (Chester); beside Hadrian's Wall around Luguvalium (Carlisle); and between the walls along Dere Street.

 

4th century

Emperor Constantius returned to Britain in 306, despite his poor health, with an army aiming to invade northern Britain, the provincial defences having been rebuilt in the preceding years. Little is known of his campaigns with scant archaeological evidence, but fragmentary historical sources suggest he reached the far north of Britain and won a major battle in early summer before returning south. His son Constantine (later Constantine the Great) spent a year in northern Britain at his father's side, campaigning against the Picts beyond Hadrian's Wall in the summer and autumn. Constantius died in York in July 306 with his son at his side. Constantine then successfully used Britain as the starting point of his march to the imperial throne, unlike the earlier usurper, Albinus.

 

In the middle of the century, the province was loyal for a few years to the usurper Magnentius, who succeeded Constans following the latter's death. After the defeat and death of Magnentius in the Battle of Mons Seleucus in 353, Constantius II dispatched his chief imperial notary Paulus Catena to Britain to hunt down Magnentius's supporters. The investigation deteriorated into a witch-hunt, which forced the vicarius Flavius Martinus to intervene. When Paulus retaliated by accusing Martinus of treason, the vicarius attacked Paulus with a sword, with the aim of assassinating him, but in the end he committed suicide.

 

As the 4th century progressed, there were increasing attacks from the Saxons in the east and the Scoti (Irish) in the west. A series of forts had been built, starting around 280, to defend the coasts, but these preparations were not enough when, in 367, a general assault of Saxons, Picts, Scoti and Attacotti, combined with apparent dissension in the garrison on Hadrian's Wall, left Roman Britain prostrate. The invaders overwhelmed the entire western and northern regions of Britannia and the cities were sacked. This crisis, sometimes called the Barbarian Conspiracy or the Great Conspiracy, was settled by Count Theodosius from 368 with a string of military and civil reforms. Theodosius crossed from Bononia (Boulogne-sur-Mer) and marched on Londinium where he began to deal with the invaders and made his base.[ An amnesty was promised to deserters which enabled Theodosius to regarrison abandoned forts. By the end of the year Hadrian's Wall was retaken and order returned. Considerable reorganization was undertaken in Britain, including the creation of a new province named Valentia, probably to better address the state of the far north. A new Dux Britanniarum was appointed, Dulcitius, with Civilis to head a new civilian administration.

 

Another imperial usurper, Magnus Maximus, raised the standard of revolt at Segontium (Caernarfon) in north Wales in 383, and crossed the English Channel. Maximus held much of the western empire, and fought a successful campaign against the Picts and Scots around 384. His continental exploits required troops from Britain, and it appears that forts at Chester and elsewhere were abandoned in this period, triggering raids and settlement in north Wales by the Irish. His rule was ended in 388, but not all the British troops may have returned: the Empire's military resources were stretched to the limit along the Rhine and Danube. Around 396 there were more barbarian incursions into Britain. Stilicho led a punitive expedition. It seems peace was restored by 399, and it is likely that no further garrisoning was ordered; by 401 more troops were withdrawn, to assist in the war against Alaric I.

 

End of Roman rule

The traditional view of historians, informed by the work of Michael Rostovtzeff, was of a widespread economic decline at the beginning of the 5th century. Consistent archaeological evidence has told another story, and the accepted view is undergoing re-evaluation. Some features are agreed: more opulent but fewer urban houses, an end to new public building and some abandonment of existing ones, with the exception of defensive structures, and the widespread formation of "dark earth" deposits indicating increased horticulture within urban precincts. Turning over the basilica at Silchester to industrial uses in the late 3rd century, doubtless officially condoned, marks an early stage in the de-urbanisation of Roman Britain.

 

The abandonment of some sites is now believed to be later than had been thought. Many buildings changed use but were not destroyed. There was a growing number of barbarian attacks, but these targeted vulnerable rural settlements rather than towns. Some villas such as Chedworth, Great Casterton in Rutland and Hucclecote in Gloucestershire had new mosaic floors laid around this time, suggesting that economic problems may have been limited and patchy. Many suffered some decay before being abandoned in the 5th century; the story of Saint Patrick indicates that villas were still occupied until at least 430. Exceptionally, new buildings were still going up in this period in Verulamium and Cirencester. Some urban centres, for example Canterbury, Cirencester, Wroxeter, Winchester and Gloucester, remained active during the 5th and 6th centuries, surrounded by large farming estates.

 

Urban life had generally grown less intense by the fourth quarter of the 4th century, and coins minted between 378 and 388 are very rare, indicating a likely combination of economic decline, diminishing numbers of troops, problems with the payment of soldiers and officials or with unstable conditions during the usurpation of Magnus Maximus 383–87. Coinage circulation increased during the 390s, but never attained the levels of earlier decades. Copper coins are very rare after 402, though minted silver and gold coins from hoards indicate they were still present in the province even if they were not being spent. By 407 there were very few new Roman coins going into circulation, and by 430 it is likely that coinage as a medium of exchange had been abandoned. Mass-produced wheel thrown pottery ended at approximately the same time; the rich continued to use metal and glass vessels, while the poor made do with humble "grey ware" or resorted to leather or wooden containers.

 

Sub-Roman Britain

Towards the end of the 4th century Roman rule in Britain came under increasing pressure from barbarian attacks. Apparently, there were not enough troops to mount an effective defence. After elevating two disappointing usurpers, the army chose a soldier, Constantine III, to become emperor in 407. He crossed to Gaul but was defeated by Honorius; it is unclear how many troops remained or ever returned, or whether a commander-in-chief in Britain was ever reappointed. A Saxon incursion in 408 was apparently repelled by the Britons, and in 409 Zosimus records that the natives expelled the Roman civilian administration. Zosimus may be referring to the Bacaudic rebellion of the Breton inhabitants of Armorica since he describes how, in the aftermath of the revolt, all of Armorica and the rest of Gaul followed the example of the Brettaniai. A letter from Emperor Honorius in 410 has traditionally been seen as rejecting a British appeal for help, but it may have been addressed to Bruttium or Bologna. With the imperial layers of the military and civil government gone, administration and justice fell to municipal authorities, and local warlords gradually emerged all over Britain, still utilizing Romano-British ideals and conventions. Historian Stuart Laycock has investigated this process and emphasised elements of continuity from the British tribes in the pre-Roman and Roman periods, through to the native post-Roman kingdoms.

 

In British tradition, pagan Saxons were invited by Vortigern to assist in fighting the Picts, Scoti, and Déisi. (Germanic migration into Roman Britannia may have begun much earlier. There is recorded evidence, for example, of Germanic auxiliaries supporting the legions in Britain in the 1st and 2nd centuries.) The new arrivals rebelled, plunging the country into a series of wars that eventually led to the Saxon occupation of Lowland Britain by 600. Around this time, many Britons fled to Brittany (hence its name), Galicia and probably Ireland. A significant date in sub-Roman Britain is the Groans of the Britons, an unanswered appeal to Aetius, leading general of the western Empire, for assistance against Saxon invasion in 446. Another is the Battle of Deorham in 577, after which the significant cities of Bath, Cirencester and Gloucester fell and the Saxons reached the western sea.

 

Historians generally reject the historicity of King Arthur, who is supposed to have resisted the Anglo-Saxon conquest according to later medieval legends.

 

Trade

During the Roman period Britain's continental trade was principally directed across the Southern North Sea and Eastern Channel, focusing on the narrow Strait of Dover, with more limited links via the Atlantic seaways. The most important British ports were London and Richborough, whilst the continental ports most heavily engaged in trade with Britain were Boulogne and the sites of Domburg and Colijnsplaat at the mouth of the river Scheldt. During the Late Roman period it is likely that the shore forts played some role in continental trade alongside their defensive functions.

 

Exports to Britain included: coin; pottery, particularly red-gloss terra sigillata (samian ware) from southern, central and eastern Gaul, as well as various other wares from Gaul and the Rhine provinces; olive oil from southern Spain in amphorae; wine from Gaul in amphorae and barrels; salted fish products from the western Mediterranean and Brittany in barrels and amphorae; preserved olives from southern Spain in amphorae; lava quern-stones from Mayen on the middle Rhine; glass; and some agricultural products. Britain's exports are harder to detect archaeologically, but will have included metals, such as silver and gold and some lead, iron and copper. Other exports probably included agricultural products, oysters and salt, whilst large quantities of coin would have been re-exported back to the continent as well.

 

These products moved as a result of private trade and also through payments and contracts established by the Roman state to support its military forces and officials on the island, as well as through state taxation and extraction of resources. Up until the mid-3rd century, the Roman state's payments appear to have been unbalanced, with far more products sent to Britain, to support its large military force (which had reached c. 53,000 by the mid-2nd century), than were extracted from the island.

 

It has been argued that Roman Britain's continental trade peaked in the late 1st century AD and thereafter declined as a result of an increasing reliance on local products by the population of Britain, caused by economic development on the island and by the Roman state's desire to save money by shifting away from expensive long-distance imports. Evidence has been outlined that suggests that the principal decline in Roman Britain's continental trade may have occurred in the late 2nd century AD, from c. 165 AD onwards. This has been linked to the economic impact of contemporary Empire-wide crises: the Antonine Plague and the Marcomannic Wars.

 

From the mid-3rd century onwards, Britain no longer received such a wide range and extensive quantity of foreign imports as it did during the earlier part of the Roman period; vast quantities of coin from continental mints reached the island, whilst there is historical evidence for the export of large amounts of British grain to the continent during the mid-4th century. During the latter part of the Roman period British agricultural products, paid for by both the Roman state and by private consumers, clearly played an important role in supporting the military garrisons and urban centres of the northwestern continental Empire. This came about as a result of the rapid decline in the size of the British garrison from the mid-3rd century onwards (thus freeing up more goods for export), and because of 'Germanic' incursions across the Rhine, which appear to have reduced rural settlement and agricultural output in northern Gaul.

 

Economy

Mineral extraction sites such as the Dolaucothi gold mine were probably first worked by the Roman army from c. 75, and at some later stage passed to civilian operators. The mine developed as a series of opencast workings, mainly by the use of hydraulic mining methods. They are described by Pliny the Elder in his Natural History in great detail. Essentially, water supplied by aqueducts was used to prospect for ore veins by stripping away soil to reveal the bedrock. If veins were present, they were attacked using fire-setting and the ore removed for comminution. The dust was washed in a small stream of water and the heavy gold dust and gold nuggets collected in riffles. The diagram at right shows how Dolaucothi developed from c. 75 through to the 1st century. When opencast work was no longer feasible, tunnels were driven to follow the veins. The evidence from the site shows advanced technology probably under the control of army engineers.

 

The Wealden ironworking zone, the lead and silver mines of the Mendip Hills and the tin mines of Cornwall seem to have been private enterprises leased from the government for a fee. Mining had long been practised in Britain (see Grimes Graves), but the Romans introduced new technical knowledge and large-scale industrial production to revolutionise the industry. It included hydraulic mining to prospect for ore by removing overburden as well as work alluvial deposits. The water needed for such large-scale operations was supplied by one or more aqueducts, those surviving at Dolaucothi being especially impressive. Many prospecting areas were in dangerous, upland country, and, although mineral exploitation was presumably one of the main reasons for the Roman invasion, it had to wait until these areas were subdued.

 

By the 3rd and 4th centuries, small towns could often be found near villas. In these towns, villa owners and small-scale farmers could obtain specialist tools. Lowland Britain in the 4th century was agriculturally prosperous enough to export grain to the continent. This prosperity lay behind the blossoming of villa building and decoration that occurred between AD 300 and 350.

 

Britain's cities also consumed Roman-style pottery and other goods, and were centres through which goods could be distributed elsewhere. At Wroxeter in Shropshire, stock smashed into a gutter during a 2nd-century fire reveals that Gaulish samian ware was being sold alongside mixing bowls from the Mancetter-Hartshill industry of the West Midlands. Roman designs were most popular, but rural craftsmen still produced items derived from the Iron Age La Tène artistic traditions. Britain was home to much gold, which attracted Roman invaders. By the 3rd century, Britain's economy was diverse and well established, with commerce extending into the non-Romanised north.

 

Government

Further information: Governors of Roman Britain, Roman client kingdoms in Britain, and Roman auxiliaries in Britain

Under the Roman Empire, administration of peaceful provinces was ultimately the remit of the Senate, but those, like Britain, that required permanent garrisons, were placed under the Emperor's control. In practice imperial provinces were run by resident governors who were members of the Senate and had held the consulship. These men were carefully selected, often having strong records of military success and administrative ability. In Britain, a governor's role was primarily military, but numerous other tasks were also his responsibility, such as maintaining diplomatic relations with local client kings, building roads, ensuring the public courier system functioned, supervising the civitates and acting as a judge in important legal cases. When not campaigning, he would travel the province hearing complaints and recruiting new troops.

 

To assist him in legal matters he had an adviser, the legatus juridicus, and those in Britain appear to have been distinguished lawyers perhaps because of the challenge of incorporating tribes into the imperial system and devising a workable method of taxing them. Financial administration was dealt with by a procurator with junior posts for each tax-raising power. Each legion in Britain had a commander who answered to the governor and, in time of war, probably directly ruled troublesome districts. Each of these commands carried a tour of duty of two to three years in different provinces. Below these posts was a network of administrative managers covering intelligence gathering, sending reports to Rome, organising military supplies and dealing with prisoners. A staff of seconded soldiers provided clerical services.

 

Colchester was probably the earliest capital of Roman Britain, but it was soon eclipsed by London with its strong mercantile connections. The different forms of municipal organisation in Britannia were known as civitas (which were subdivided, amongst other forms, into colonies such as York, Colchester, Gloucester and Lincoln and municipalities such as Verulamium), and were each governed by a senate of local landowners, whether Brythonic or Roman, who elected magistrates concerning judicial and civic affairs. The various civitates sent representatives to a yearly provincial council in order to profess loyalty to the Roman state, to send direct petitions to the Emperor in times of extraordinary need, and to worship the imperial cult.

 

Demographics

Roman Britain had an estimated population between 2.8 million and 3 million people at the end of the second century. At the end of the fourth century, it had an estimated population of 3.6 million people, of whom 125,000 consisted of the Roman army and their families and dependents.[80] The urban population of Roman Britain was about 240,000 people at the end of the fourth century. The capital city of Londinium is estimated to have had a population of about 60,000 people. Londinium was an ethnically diverse city with inhabitants from the Roman Empire, including natives of Britannia, continental Europe, the Middle East, and North Africa. There was also cultural diversity in other Roman-British towns, which were sustained by considerable migration, from Britannia and other Roman territories, including continental Europe, Roman Syria, the Eastern Mediterranean and North Africa. In a study conducted in 2012, around 45 percent of sites investigated dating from the Roman period had at least one individual of North African origin.

 

Town and country

During their occupation of Britain the Romans founded a number of important settlements, many of which survive. The towns suffered attrition in the later 4th century, when public building ceased and some were abandoned to private uses. Place names survived the deurbanised Sub-Roman and early Anglo-Saxon periods, and historiography has been at pains to signal the expected survivals, but archaeology shows that a bare handful of Roman towns were continuously occupied. According to S.T. Loseby, the very idea of a town as a centre of power and administration was reintroduced to England by the Roman Christianising mission to Canterbury, and its urban revival was delayed to the 10th century.

 

Roman towns can be broadly grouped in two categories. Civitates, "public towns" were formally laid out on a grid plan, and their role in imperial administration occasioned the construction of public buildings. The much more numerous category of vici, "small towns" grew on informal plans, often round a camp or at a ford or crossroads; some were not small, others were scarcely urban, some not even defended by a wall, the characteristic feature of a place of any importance.

 

Cities and towns which have Roman origins, or were extensively developed by them are listed with their Latin names in brackets; civitates are marked C

 

Alcester (Alauna)

Alchester

Aldborough, North Yorkshire (Isurium Brigantum) C

Bath (Aquae Sulis) C

Brough (Petuaria) C

Buxton (Aquae Arnemetiae)

Caerleon (Isca Augusta) C

Caernarfon (Segontium) C

Caerwent (Venta Silurum) C

Caister-on-Sea C

Canterbury (Durovernum Cantiacorum) C

Carlisle (Luguvalium) C

Carmarthen (Moridunum) C

Chelmsford (Caesaromagus)

Chester (Deva Victrix) C

Chester-le-Street (Concangis)

Chichester (Noviomagus Reginorum) C

Cirencester (Corinium) C

Colchester (Camulodunum) C

Corbridge (Coria) C

Dorchester (Durnovaria) C

Dover (Portus Dubris)

Exeter (Isca Dumnoniorum) C

Gloucester (Glevum) C

Great Chesterford (the name of this vicus is unknown)

Ilchester (Lindinis) C

Leicester (Ratae Corieltauvorum) C

Lincoln (Lindum Colonia) C

London (Londinium) C

Manchester (Mamucium) C

Newcastle upon Tyne (Pons Aelius)

Northwich (Condate)

St Albans (Verulamium) C

Silchester (Calleva Atrebatum) C

Towcester (Lactodurum)

Whitchurch (Mediolanum) C

Winchester (Venta Belgarum) C

Wroxeter (Viroconium Cornoviorum) C

York (Eboracum) C

 

Religion

The druids, the Celtic priestly caste who were believed to originate in Britain, were outlawed by Claudius, and in 61 they vainly defended their sacred groves from destruction by the Romans on the island of Mona (Anglesey). Under Roman rule the Britons continued to worship native Celtic deities, such as Ancasta, but often conflated with their Roman equivalents, like Mars Rigonemetos at Nettleham.

 

The degree to which earlier native beliefs survived is difficult to gauge precisely. Certain European ritual traits such as the significance of the number 3, the importance of the head and of water sources such as springs remain in the archaeological record, but the differences in the votive offerings made at the baths at Bath, Somerset, before and after the Roman conquest suggest that continuity was only partial. Worship of the Roman emperor is widely recorded, especially at military sites. The founding of a Roman temple to Claudius at Camulodunum was one of the impositions that led to the revolt of Boudica. By the 3rd century, Pagans Hill Roman Temple in Somerset was able to exist peaceably and it did so into the 5th century.

 

Pagan religious practices were supported by priests, represented in Britain by votive deposits of priestly regalia such as chain crowns from West Stow and Willingham Fen.

 

Eastern cults such as Mithraism also grew in popularity towards the end of the occupation. The London Mithraeum is one example of the popularity of mystery religions among the soldiery. Temples to Mithras also exist in military contexts at Vindobala on Hadrian's Wall (the Rudchester Mithraeum) and at Segontium in Roman Wales (the Caernarfon Mithraeum).

 

Christianity

It is not clear when or how Christianity came to Britain. A 2nd-century "word square" has been discovered in Mamucium, the Roman settlement of Manchester. It consists of an anagram of PATER NOSTER carved on a piece of amphora. There has been discussion by academics whether the "word square" is a Christian artefact, but if it is, it is one of the earliest examples of early Christianity in Britain. The earliest confirmed written evidence for Christianity in Britain is a statement by Tertullian, c. 200 AD, in which he described "all the limits of the Spains, and the diverse nations of the Gauls, and the haunts of the Britons, inaccessible to the Romans, but subjugated to Christ". Archaeological evidence for Christian communities begins to appear in the 3rd and 4th centuries. Small timber churches are suggested at Lincoln and Silchester and baptismal fonts have been found at Icklingham and the Saxon Shore Fort at Richborough. The Icklingham font is made of lead, and visible in the British Museum. A Roman Christian graveyard exists at the same site in Icklingham. A possible Roman 4th-century church and associated burial ground was also discovered at Butt Road on the south-west outskirts of Colchester during the construction of the new police station there, overlying an earlier pagan cemetery. The Water Newton Treasure is a hoard of Christian silver church plate from the early 4th century and the Roman villas at Lullingstone and Hinton St Mary contained Christian wall paintings and mosaics respectively. A large 4th-century cemetery at Poundbury with its east–west oriented burials and lack of grave goods has been interpreted as an early Christian burial ground, although such burial rites were also becoming increasingly common in pagan contexts during the period.

 

The Church in Britain seems to have developed the customary diocesan system, as evidenced from the records of the Council of Arles in Gaul in 314: represented at the council were bishops from thirty-five sees from Europe and North Africa, including three bishops from Britain, Eborius of York, Restitutus of London, and Adelphius, possibly a bishop of Lincoln. No other early sees are documented, and the material remains of early church structures are far to seek. The existence of a church in the forum courtyard of Lincoln and the martyrium of Saint Alban on the outskirts of Roman Verulamium are exceptional. Alban, the first British Christian martyr and by far the most prominent, is believed to have died in the early 4th century (some date him in the middle 3rd century), followed by Saints Julius and Aaron of Isca Augusta. Christianity was legalised in the Roman Empire by Constantine I in 313. Theodosius I made Christianity the state religion of the empire in 391, and by the 5th century it was well established. One belief labelled a heresy by the church authorities — Pelagianism — was originated by a British monk teaching in Rome: Pelagius lived c. 354 to c. 420/440.

 

A letter found on a lead tablet in Bath, Somerset, datable to c. 363, had been widely publicised as documentary evidence regarding the state of Christianity in Britain during Roman times. According to its first translator, it was written in Wroxeter by a Christian man called Vinisius to a Christian woman called Nigra, and was claimed as the first epigraphic record of Christianity in Britain. This translation of the letter was apparently based on grave paleographical errors, and the text has nothing to do with Christianity, and in fact relates to pagan rituals.

 

Environmental changes

The Romans introduced a number of species to Britain, including possibly the now-rare Roman nettle (Urtica pilulifera), said to have been used by soldiers to warm their arms and legs, and the edible snail Helix pomatia. There is also some evidence they may have introduced rabbits, but of the smaller southern mediterranean type. The European rabbit (Oryctolagus cuniculus) prevalent in modern Britain is assumed to have been introduced from the continent after the Norman invasion of 1066. Box (Buxus sempervirens) is rarely recorded before the Roman period, but becomes a common find in towns and villas

 

Legacy

During their occupation of Britain the Romans built an extensive network of roads which continued to be used in later centuries and many are still followed today. The Romans also built water supply, sanitation and wastewater systems. Many of Britain's major cities, such as London (Londinium), Manchester (Mamucium) and York (Eboracum), were founded by the Romans, but the original Roman settlements were abandoned not long after the Romans left.

 

Unlike many other areas of the Western Roman Empire, the current majority language is not a Romance language, or a language descended from the pre-Roman inhabitants. The British language at the time of the invasion was Common Brittonic, and remained so after the Romans withdrew. It later split into regional languages, notably Cumbric, Cornish, Breton and Welsh. Examination of these languages suggests some 800 Latin words were incorporated into Common Brittonic (see Brittonic languages). The current majority language, English, is based on the languages of the Germanic tribes who migrated to the island from continental Europe

White Pine Blister Rust is a fungal pathogen of five-needle pines native to China. It was introduced into North America around 1900.

"I came across a tree where a couple limbs had been cut off, and when I downloaded the image, I noticed the new growth around the inside edges of where the branches had been removed. Don't think I'd ever seen this before so....I GOOGLED IT !!! Here's what I found out....." Trees respond to wounding or injury in two ways: compartmentalization and the development of barrier zones. Compartmentalization: When a tree is wounded, the injured tissue is not repaired and does not heal. Trees do not heal; they seal. If you look at an old wound, you will notice that it does not “heal” from the inside out, but eventually the tree covers the opening by forming specialized “callus” tissue around the edges of the wound. After wounding, new wood growing around the wound forms a protective boundary preventing the infection or decay from spreading into the new tissue. Thus, the tree responds to the injury by “compartmentalizing” or isolating the older, injured tissue with the gradual growth of new, healthy tissue. Barrier Zones: Not only do trees try to close the damaged tissue from the outside, they also make the existing wood surrounding the wound unsuitable for spread of decay organisms. Although these processes are not well understood, the tree tries to avoid further injury by setting chemical and physical boundaries around the infected cells, reacting to the pathogen and confining the damage. "WOW....Who knew?"

  

Order: Unassigned

Family: Virgaviridae

Genus: Tobamovirus

 

(+)ssRNA

 

***

 

English: Tobacco mosaic disease

 

Deutsch: Tabakosaikkrankheit

 

Magyar: Dohánymozaik betegség

 

Français: Maladie de la mosaïque du tabac

 

Español: Enfermedad del mosaico del tabaco

A fungus (pl.: fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the traditional eukaryotic kingdoms, along with Animalia, Plantae and either Protista or Protozoa and Chromista.

 

A characteristic that places fungi in a different kingdom from plants, bacteria, and some protists is chitin in their cell walls. Fungi, like animals, are heterotrophs; they acquire their food by absorbing dissolved molecules, typically by secreting digestive enzymes into their environment. Fungi do not photosynthesize. Growth is their means of mobility, except for spores (a few of which are flagellated), which may travel through the air or water. Fungi are the principal decomposers in ecological systems. These and other differences place fungi in a single group of related organisms, named the Eumycota (true fungi or Eumycetes), that share a common ancestor (i.e. they form a monophyletic group), an interpretation that is also strongly supported by molecular phylogenetics. This fungal group is distinct from the structurally similar myxomycetes (slime molds) and oomycetes (water molds). The discipline of biology devoted to the study of fungi is known as mycology (from the Greek μύκης mykes, mushroom). In the past mycology was regarded as a branch of botany, although it is now known that fungi are genetically more closely related to animals than to plants.

 

Abundant worldwide, most fungi are inconspicuous because of the small size of their structures, and their cryptic lifestyles in soil or on dead matter. Fungi include symbionts of plants, animals, or other fungi and also parasites. They may become noticeable when fruiting, either as mushrooms or as molds. Fungi perform an essential role in the decomposition of organic matter and have fundamental roles in nutrient cycling and exchange in the environment. They have long been used as a direct source of human food, in the form of mushrooms and truffles; as a leavening agent for bread; and in the fermentation of various food products, such as wine, beer, and soy sauce. Since the 1940s, fungi have been used for the production of antibiotics, and, more recently, various enzymes produced by fungi are used industrially and in detergents. Fungi are also used as biological pesticides to control weeds, plant diseases, and insect pests. Many species produce bioactive compounds called mycotoxins, such as alkaloids and polyketides, that are toxic to animals, including humans. The fruiting structures of a few species contain psychotropic compounds and are consumed recreationally or in traditional spiritual ceremonies. Fungi can break down manufactured materials and buildings, and become significant pathogens of humans and other animals. Losses of crops due to fungal diseases (e.g., rice blast disease) or food spoilage can have a large impact on human food supplies and local economies.

 

The fungus kingdom encompasses an enormous diversity of taxa with varied ecologies, life cycle strategies, and morphologies ranging from unicellular aquatic chytrids to large mushrooms. However, little is known of the true biodiversity of the fungus kingdom, which has been estimated at 2.2 million to 3.8 million species. Of these, only about 148,000 have been described, with over 8,000 species known to be detrimental to plants and at least 300 that can be pathogenic to humans. Ever since the pioneering 18th and 19th century taxonomical works of Carl Linnaeus, Christiaan Hendrik Persoon, and Elias Magnus Fries, fungi have been classified according to their morphology (e.g., characteristics such as spore color or microscopic features) or physiology. Advances in molecular genetics have opened the way for DNA analysis to be incorporated into taxonomy, which has sometimes challenged the historical groupings based on morphology and other traits. Phylogenetic studies published in the first decade of the 21st century have helped reshape the classification within the fungi kingdom, which is divided into one subkingdom, seven phyla, and ten subphyla.

 

Etymology

The English word fungus is directly adopted from the Latin fungus (mushroom), used in the writings of Horace and Pliny. This in turn is derived from the Greek word sphongos (σφόγγος 'sponge'), which refers to the macroscopic structures and morphology of mushrooms and molds; the root is also used in other languages, such as the German Schwamm ('sponge') and Schimmel ('mold').

 

The word mycology is derived from the Greek mykes (μύκης 'mushroom') and logos (λόγος 'discourse'). It denotes the scientific study of fungi. The Latin adjectival form of "mycology" (mycologicæ) appeared as early as 1796 in a book on the subject by Christiaan Hendrik Persoon. The word appeared in English as early as 1824 in a book by Robert Kaye Greville. In 1836 the English naturalist Miles Joseph Berkeley's publication The English Flora of Sir James Edward Smith, Vol. 5. also refers to mycology as the study of fungi.

 

A group of all the fungi present in a particular region is known as mycobiota (plural noun, no singular). The term mycota is often used for this purpose, but many authors use it as a synonym of Fungi. The word funga has been proposed as a less ambiguous term morphologically similar to fauna and flora. The Species Survival Commission (SSC) of the International Union for Conservation of Nature (IUCN) in August 2021 asked that the phrase fauna and flora be replaced by fauna, flora, and funga.

 

Characteristics

 

Fungal hyphae cells

Hyphal wall

Septum

Mitochondrion

Vacuole

Ergosterol crystal

Ribosome

Nucleus

Endoplasmic reticulum

Lipid body

Plasma membrane

Spitzenkörper

Golgi apparatus

 

Fungal cell cycle showing Dikaryons typical of Higher Fungi

Before the introduction of molecular methods for phylogenetic analysis, taxonomists considered fungi to be members of the plant kingdom because of similarities in lifestyle: both fungi and plants are mainly immobile, and have similarities in general morphology and growth habitat. Although inaccurate, the common misconception that fungi are plants persists among the general public due to their historical classification, as well as several similarities. Like plants, fungi often grow in soil and, in the case of mushrooms, form conspicuous fruit bodies, which sometimes resemble plants such as mosses. The fungi are now considered a separate kingdom, distinct from both plants and animals, from which they appear to have diverged around one billion years ago (around the start of the Neoproterozoic Era). Some morphological, biochemical, and genetic features are shared with other organisms, while others are unique to the fungi, clearly separating them from the other kingdoms:

 

With other eukaryotes: Fungal cells contain membrane-bound nuclei with chromosomes that contain DNA with noncoding regions called introns and coding regions called exons. Fungi have membrane-bound cytoplasmic organelles such as mitochondria, sterol-containing membranes, and ribosomes of the 80S type. They have a characteristic range of soluble carbohydrates and storage compounds, including sugar alcohols (e.g., mannitol), disaccharides, (e.g., trehalose), and polysaccharides (e.g., glycogen, which is also found in animals).

With animals: Fungi lack chloroplasts and are heterotrophic organisms and so require preformed organic compounds as energy sources.

With plants: Fungi have a cell wall and vacuoles. They reproduce by both sexual and asexual means, and like basal plant groups (such as ferns and mosses) produce spores. Similar to mosses and algae, fungi typically have haploid nuclei.

With euglenoids and bacteria: Higher fungi, euglenoids, and some bacteria produce the amino acid L-lysine in specific biosynthesis steps, called the α-aminoadipate pathway.

The cells of most fungi grow as tubular, elongated, and thread-like (filamentous) structures called hyphae, which may contain multiple nuclei and extend by growing at their tips. Each tip contains a set of aggregated vesicles—cellular structures consisting of proteins, lipids, and other organic molecules—called the Spitzenkörper. Both fungi and oomycetes grow as filamentous hyphal cells. In contrast, similar-looking organisms, such as filamentous green algae, grow by repeated cell division within a chain of cells. There are also single-celled fungi (yeasts) that do not form hyphae, and some fungi have both hyphal and yeast forms.

In common with some plant and animal species, more than one hundred fungal species display bioluminescence.

Unique features:

 

Some species grow as unicellular yeasts that reproduce by budding or fission. Dimorphic fungi can switch between a yeast phase and a hyphal phase in response to environmental conditions.

The fungal cell wall is made of a chitin-glucan complex; while glucans are also found in plants and chitin in the exoskeleton of arthropods, fungi are the only organisms that combine these two structural molecules in their cell wall. Unlike those of plants and oomycetes, fungal cell walls do not contain cellulose.

A whitish fan or funnel-shaped mushroom growing at the base of a tree.

Omphalotus nidiformis, a bioluminescent mushroom

Most fungi lack an efficient system for the long-distance transport of water and nutrients, such as the xylem and phloem in many plants. To overcome this limitation, some fungi, such as Armillaria, form rhizomorphs, which resemble and perform functions similar to the roots of plants. As eukaryotes, fungi possess a biosynthetic pathway for producing terpenes that uses mevalonic acid and pyrophosphate as chemical building blocks. Plants and some other organisms have an additional terpene biosynthesis pathway in their chloroplasts, a structure that fungi and animals do not have. Fungi produce several secondary metabolites that are similar or identical in structure to those made by plants. Many of the plant and fungal enzymes that make these compounds differ from each other in sequence and other characteristics, which indicates separate origins and convergent evolution of these enzymes in the fungi and plants.

 

Diversity

Fungi have a worldwide distribution, and grow in a wide range of habitats, including extreme environments such as deserts or areas with high salt concentrations or ionizing radiation, as well as in deep sea sediments. Some can survive the intense UV and cosmic radiation encountered during space travel. Most grow in terrestrial environments, though several species live partly or solely in aquatic habitats, such as the chytrid fungi Batrachochytrium dendrobatidis and B. salamandrivorans, parasites that have been responsible for a worldwide decline in amphibian populations. These organisms spend part of their life cycle as a motile zoospore, enabling them to propel itself through water and enter their amphibian host. Other examples of aquatic fungi include those living in hydrothermal areas of the ocean.

 

As of 2020, around 148,000 species of fungi have been described by taxonomists, but the global biodiversity of the fungus kingdom is not fully understood. A 2017 estimate suggests there may be between 2.2 and 3.8 million species The number of new fungi species discovered yearly has increased from 1,000 to 1,500 per year about 10 years ago, to about 2000 with a peak of more than 2,500 species in 2016. In the year 2019, 1882 new species of fungi were described, and it was estimated that more than 90% of fungi remain unknown The following year, 2905 new species were described—the highest annual record of new fungus names. In mycology, species have historically been distinguished by a variety of methods and concepts. Classification based on morphological characteristics, such as the size and shape of spores or fruiting structures, has traditionally dominated fungal taxonomy. Species may also be distinguished by their biochemical and physiological characteristics, such as their ability to metabolize certain biochemicals, or their reaction to chemical tests. The biological species concept discriminates species based on their ability to mate. The application of molecular tools, such as DNA sequencing and phylogenetic analysis, to study diversity has greatly enhanced the resolution and added robustness to estimates of genetic diversity within various taxonomic groups.

 

Mycology

Mycology is the branch of biology concerned with the systematic study of fungi, including their genetic and biochemical properties, their taxonomy, and their use to humans as a source of medicine, food, and psychotropic substances consumed for religious purposes, as well as their dangers, such as poisoning or infection. The field of phytopathology, the study of plant diseases, is closely related because many plant pathogens are fungi.

 

The use of fungi by humans dates back to prehistory; Ötzi the Iceman, a well-preserved mummy of a 5,300-year-old Neolithic man found frozen in the Austrian Alps, carried two species of polypore mushrooms that may have been used as tinder (Fomes fomentarius), or for medicinal purposes (Piptoporus betulinus). Ancient peoples have used fungi as food sources—often unknowingly—for millennia, in the preparation of leavened bread and fermented juices. Some of the oldest written records contain references to the destruction of crops that were probably caused by pathogenic fungi.

 

History

Mycology became a systematic science after the development of the microscope in the 17th century. Although fungal spores were first observed by Giambattista della Porta in 1588, the seminal work in the development of mycology is considered to be the publication of Pier Antonio Micheli's 1729 work Nova plantarum genera. Micheli not only observed spores but also showed that, under the proper conditions, they could be induced into growing into the same species of fungi from which they originated. Extending the use of the binomial system of nomenclature introduced by Carl Linnaeus in his Species plantarum (1753), the Dutch Christiaan Hendrik Persoon (1761–1836) established the first classification of mushrooms with such skill as to be considered a founder of modern mycology. Later, Elias Magnus Fries (1794–1878) further elaborated the classification of fungi, using spore color and microscopic characteristics, methods still used by taxonomists today. Other notable early contributors to mycology in the 17th–19th and early 20th centuries include Miles Joseph Berkeley, August Carl Joseph Corda, Anton de Bary, the brothers Louis René and Charles Tulasne, Arthur H. R. Buller, Curtis G. Lloyd, and Pier Andrea Saccardo. In the 20th and 21st centuries, advances in biochemistry, genetics, molecular biology, biotechnology, DNA sequencing and phylogenetic analysis has provided new insights into fungal relationships and biodiversity, and has challenged traditional morphology-based groupings in fungal taxonomy.

 

Morphology

Microscopic structures

Monochrome micrograph showing Penicillium hyphae as long, transparent, tube-like structures a few micrometres across. Conidiophores branch out laterally from the hyphae, terminating in bundles of phialides on which spherical condidiophores are arranged like beads on a string. Septa are faintly visible as dark lines crossing the hyphae.

An environmental isolate of Penicillium

Hypha

Conidiophore

Phialide

Conidia

Septa

Most fungi grow as hyphae, which are cylindrical, thread-like structures 2–10 µm in diameter and up to several centimeters in length. Hyphae grow at their tips (apices); new hyphae are typically formed by emergence of new tips along existing hyphae by a process called branching, or occasionally growing hyphal tips fork, giving rise to two parallel-growing hyphae. Hyphae also sometimes fuse when they come into contact, a process called hyphal fusion (or anastomosis). These growth processes lead to the development of a mycelium, an interconnected network of hyphae. Hyphae can be either septate or coenocytic. Septate hyphae are divided into compartments separated by cross walls (internal cell walls, called septa, that are formed at right angles to the cell wall giving the hypha its shape), with each compartment containing one or more nuclei; coenocytic hyphae are not compartmentalized. Septa have pores that allow cytoplasm, organelles, and sometimes nuclei to pass through; an example is the dolipore septum in fungi of the phylum Basidiomycota. Coenocytic hyphae are in essence multinucleate supercells.

 

Many species have developed specialized hyphal structures for nutrient uptake from living hosts; examples include haustoria in plant-parasitic species of most fungal phyla,[63] and arbuscules of several mycorrhizal fungi, which penetrate into the host cells to consume nutrients.

 

Although fungi are opisthokonts—a grouping of evolutionarily related organisms broadly characterized by a single posterior flagellum—all phyla except for the chytrids have lost their posterior flagella. Fungi are unusual among the eukaryotes in having a cell wall that, in addition to glucans (e.g., β-1,3-glucan) and other typical components, also contains the biopolymer chitin.

 

Macroscopic structures

Fungal mycelia can become visible to the naked eye, for example, on various surfaces and substrates, such as damp walls and spoiled food, where they are commonly called molds. Mycelia grown on solid agar media in laboratory petri dishes are usually referred to as colonies. These colonies can exhibit growth shapes and colors (due to spores or pigmentation) that can be used as diagnostic features in the identification of species or groups. Some individual fungal colonies can reach extraordinary dimensions and ages as in the case of a clonal colony of Armillaria solidipes, which extends over an area of more than 900 ha (3.5 square miles), with an estimated age of nearly 9,000 years.

 

The apothecium—a specialized structure important in sexual reproduction in the ascomycetes—is a cup-shaped fruit body that is often macroscopic and holds the hymenium, a layer of tissue containing the spore-bearing cells. The fruit bodies of the basidiomycetes (basidiocarps) and some ascomycetes can sometimes grow very large, and many are well known as mushrooms.

 

Growth and physiology

Time-lapse photography sequence of a peach becoming progressively discolored and disfigured

Mold growth covering a decaying peach. The frames were taken approximately 12 hours apart over a period of six days.

The growth of fungi as hyphae on or in solid substrates or as single cells in aquatic environments is adapted for the efficient extraction of nutrients, because these growth forms have high surface area to volume ratios. Hyphae are specifically adapted for growth on solid surfaces, and to invade substrates and tissues. They can exert large penetrative mechanical forces; for example, many plant pathogens, including Magnaporthe grisea, form a structure called an appressorium that evolved to puncture plant tissues.[71] The pressure generated by the appressorium, directed against the plant epidermis, can exceed 8 megapascals (1,200 psi).[71] The filamentous fungus Paecilomyces lilacinus uses a similar structure to penetrate the eggs of nematodes.

 

The mechanical pressure exerted by the appressorium is generated from physiological processes that increase intracellular turgor by producing osmolytes such as glycerol. Adaptations such as these are complemented by hydrolytic enzymes secreted into the environment to digest large organic molecules—such as polysaccharides, proteins, and lipids—into smaller molecules that may then be absorbed as nutrients. The vast majority of filamentous fungi grow in a polar fashion (extending in one direction) by elongation at the tip (apex) of the hypha. Other forms of fungal growth include intercalary extension (longitudinal expansion of hyphal compartments that are below the apex) as in the case of some endophytic fungi, or growth by volume expansion during the development of mushroom stipes and other large organs. Growth of fungi as multicellular structures consisting of somatic and reproductive cells—a feature independently evolved in animals and plants—has several functions, including the development of fruit bodies for dissemination of sexual spores (see above) and biofilms for substrate colonization and intercellular communication.

 

Fungi are traditionally considered heterotrophs, organisms that rely solely on carbon fixed by other organisms for metabolism. Fungi have evolved a high degree of metabolic versatility that allows them to use a diverse range of organic substrates for growth, including simple compounds such as nitrate, ammonia, acetate, or ethanol. In some species the pigment melanin may play a role in extracting energy from ionizing radiation, such as gamma radiation. This form of "radiotrophic" growth has been described for only a few species, the effects on growth rates are small, and the underlying biophysical and biochemical processes are not well known. This process might bear similarity to CO2 fixation via visible light, but instead uses ionizing radiation as a source of energy.

 

Reproduction

Two thickly stemmed brownish mushrooms with scales on the upper surface, growing out of a tree trunk

Polyporus squamosus

Fungal reproduction is complex, reflecting the differences in lifestyles and genetic makeup within this diverse kingdom of organisms. It is estimated that a third of all fungi reproduce using more than one method of propagation; for example, reproduction may occur in two well-differentiated stages within the life cycle of a species, the teleomorph (sexual reproduction) and the anamorph (asexual reproduction). Environmental conditions trigger genetically determined developmental states that lead to the creation of specialized structures for sexual or asexual reproduction. These structures aid reproduction by efficiently dispersing spores or spore-containing propagules.

 

Asexual reproduction

Asexual reproduction occurs via vegetative spores (conidia) or through mycelial fragmentation. Mycelial fragmentation occurs when a fungal mycelium separates into pieces, and each component grows into a separate mycelium. Mycelial fragmentation and vegetative spores maintain clonal populations adapted to a specific niche, and allow more rapid dispersal than sexual reproduction. The "Fungi imperfecti" (fungi lacking the perfect or sexual stage) or Deuteromycota comprise all the species that lack an observable sexual cycle. Deuteromycota (alternatively known as Deuteromycetes, conidial fungi, or mitosporic fungi) is not an accepted taxonomic clade and is now taken to mean simply fungi that lack a known sexual stage.

 

Sexual reproduction

See also: Mating in fungi and Sexual selection in fungi

Sexual reproduction with meiosis has been directly observed in all fungal phyla except Glomeromycota (genetic analysis suggests meiosis in Glomeromycota as well). It differs in many aspects from sexual reproduction in animals or plants. Differences also exist between fungal groups and can be used to discriminate species by morphological differences in sexual structures and reproductive strategies. Mating experiments between fungal isolates may identify species on the basis of biological species concepts. The major fungal groupings have initially been delineated based on the morphology of their sexual structures and spores; for example, the spore-containing structures, asci and basidia, can be used in the identification of ascomycetes and basidiomycetes, respectively. Fungi employ two mating systems: heterothallic species allow mating only between individuals of the opposite mating type, whereas homothallic species can mate, and sexually reproduce, with any other individual or itself.

 

Most fungi have both a haploid and a diploid stage in their life cycles. In sexually reproducing fungi, compatible individuals may combine by fusing their hyphae together into an interconnected network; this process, anastomosis, is required for the initiation of the sexual cycle. Many ascomycetes and basidiomycetes go through a dikaryotic stage, in which the nuclei inherited from the two parents do not combine immediately after cell fusion, but remain separate in the hyphal cells (see heterokaryosis).

 

In ascomycetes, dikaryotic hyphae of the hymenium (the spore-bearing tissue layer) form a characteristic hook (crozier) at the hyphal septum. During cell division, the formation of the hook ensures proper distribution of the newly divided nuclei into the apical and basal hyphal compartments. An ascus (plural asci) is then formed, in which karyogamy (nuclear fusion) occurs. Asci are embedded in an ascocarp, or fruiting body. Karyogamy in the asci is followed immediately by meiosis and the production of ascospores. After dispersal, the ascospores may germinate and form a new haploid mycelium.

 

Sexual reproduction in basidiomycetes is similar to that of the ascomycetes. Compatible haploid hyphae fuse to produce a dikaryotic mycelium. However, the dikaryotic phase is more extensive in the basidiomycetes, often also present in the vegetatively growing mycelium. A specialized anatomical structure, called a clamp connection, is formed at each hyphal septum. As with the structurally similar hook in the ascomycetes, the clamp connection in the basidiomycetes is required for controlled transfer of nuclei during cell division, to maintain the dikaryotic stage with two genetically different nuclei in each hyphal compartment. A basidiocarp is formed in which club-like structures known as basidia generate haploid basidiospores after karyogamy and meiosis. The most commonly known basidiocarps are mushrooms, but they may also take other forms (see Morphology section).

 

In fungi formerly classified as Zygomycota, haploid hyphae of two individuals fuse, forming a gametangium, a specialized cell structure that becomes a fertile gamete-producing cell. The gametangium develops into a zygospore, a thick-walled spore formed by the union of gametes. When the zygospore germinates, it undergoes meiosis, generating new haploid hyphae, which may then form asexual sporangiospores. These sporangiospores allow the fungus to rapidly disperse and germinate into new genetically identical haploid fungal mycelia.

 

Spore dispersal

The spores of most of the researched species of fungi are transported by wind. Such species often produce dry or hydrophobic spores that do not absorb water and are readily scattered by raindrops, for example. In other species, both asexual and sexual spores or sporangiospores are often actively dispersed by forcible ejection from their reproductive structures. This ejection ensures exit of the spores from the reproductive structures as well as traveling through the air over long distances.

 

Specialized mechanical and physiological mechanisms, as well as spore surface structures (such as hydrophobins), enable efficient spore ejection. For example, the structure of the spore-bearing cells in some ascomycete species is such that the buildup of substances affecting cell volume and fluid balance enables the explosive discharge of spores into the air. The forcible discharge of single spores termed ballistospores involves formation of a small drop of water (Buller's drop), which upon contact with the spore leads to its projectile release with an initial acceleration of more than 10,000 g; the net result is that the spore is ejected 0.01–0.02 cm, sufficient distance for it to fall through the gills or pores into the air below. Other fungi, like the puffballs, rely on alternative mechanisms for spore release, such as external mechanical forces. The hydnoid fungi (tooth fungi) produce spores on pendant, tooth-like or spine-like projections. The bird's nest fungi use the force of falling water drops to liberate the spores from cup-shaped fruiting bodies. Another strategy is seen in the stinkhorns, a group of fungi with lively colors and putrid odor that attract insects to disperse their spores.

 

Homothallism

In homothallic sexual reproduction, two haploid nuclei derived from the same individual fuse to form a zygote that can then undergo meiosis. Homothallic fungi include species with an Aspergillus-like asexual stage (anamorphs) occurring in numerous different genera, several species of the ascomycete genus Cochliobolus, and the ascomycete Pneumocystis jirovecii. The earliest mode of sexual reproduction among eukaryotes was likely homothallism, that is, self-fertile unisexual reproduction.

 

Other sexual processes

Besides regular sexual reproduction with meiosis, certain fungi, such as those in the genera Penicillium and Aspergillus, may exchange genetic material via parasexual processes, initiated by anastomosis between hyphae and plasmogamy of fungal cells. The frequency and relative importance of parasexual events is unclear and may be lower than other sexual processes. It is known to play a role in intraspecific hybridization and is likely required for hybridization between species, which has been associated with major events in fungal evolution.

 

Evolution

In contrast to plants and animals, the early fossil record of the fungi is meager. Factors that likely contribute to the under-representation of fungal species among fossils include the nature of fungal fruiting bodies, which are soft, fleshy, and easily degradable tissues and the microscopic dimensions of most fungal structures, which therefore are not readily evident. Fungal fossils are difficult to distinguish from those of other microbes, and are most easily identified when they resemble extant fungi. Often recovered from a permineralized plant or animal host, these samples are typically studied by making thin-section preparations that can be examined with light microscopy or transmission electron microscopy. Researchers study compression fossils by dissolving the surrounding matrix with acid and then using light or scanning electron microscopy to examine surface details.

 

The earliest fossils possessing features typical of fungi date to the Paleoproterozoic era, some 2,400 million years ago (Ma); these multicellular benthic organisms had filamentous structures capable of anastomosis. Other studies (2009) estimate the arrival of fungal organisms at about 760–1060 Ma on the basis of comparisons of the rate of evolution in closely related groups. The oldest fossilizied mycelium to be identified from its molecular composition is between 715 and 810 million years old. For much of the Paleozoic Era (542–251 Ma), the fungi appear to have been aquatic and consisted of organisms similar to the extant chytrids in having flagellum-bearing spores. The evolutionary adaptation from an aquatic to a terrestrial lifestyle necessitated a diversification of ecological strategies for obtaining nutrients, including parasitism, saprobism, and the development of mutualistic relationships such as mycorrhiza and lichenization. Studies suggest that the ancestral ecological state of the Ascomycota was saprobism, and that independent lichenization events have occurred multiple times.

 

In May 2019, scientists reported the discovery of a fossilized fungus, named Ourasphaira giraldae, in the Canadian Arctic, that may have grown on land a billion years ago, well before plants were living on land. Pyritized fungus-like microfossils preserved in the basal Ediacaran Doushantuo Formation (~635 Ma) have been reported in South China. Earlier, it had been presumed that the fungi colonized the land during the Cambrian (542–488.3 Ma), also long before land plants. Fossilized hyphae and spores recovered from the Ordovician of Wisconsin (460 Ma) resemble modern-day Glomerales, and existed at a time when the land flora likely consisted of only non-vascular bryophyte-like plants. Prototaxites, which was probably a fungus or lichen, would have been the tallest organism of the late Silurian and early Devonian. Fungal fossils do not become common and uncontroversial until the early Devonian (416–359.2 Ma), when they occur abundantly in the Rhynie chert, mostly as Zygomycota and Chytridiomycota. At about this same time, approximately 400 Ma, the Ascomycota and Basidiomycota diverged, and all modern classes of fungi were present by the Late Carboniferous (Pennsylvanian, 318.1–299 Ma).

 

Lichens formed a component of the early terrestrial ecosystems, and the estimated age of the oldest terrestrial lichen fossil is 415 Ma; this date roughly corresponds to the age of the oldest known sporocarp fossil, a Paleopyrenomycites species found in the Rhynie Chert. The oldest fossil with microscopic features resembling modern-day basidiomycetes is Palaeoancistrus, found permineralized with a fern from the Pennsylvanian. Rare in the fossil record are the Homobasidiomycetes (a taxon roughly equivalent to the mushroom-producing species of the Agaricomycetes). Two amber-preserved specimens provide evidence that the earliest known mushroom-forming fungi (the extinct species Archaeomarasmius leggetti) appeared during the late Cretaceous, 90 Ma.

 

Some time after the Permian–Triassic extinction event (251.4 Ma), a fungal spike (originally thought to be an extraordinary abundance of fungal spores in sediments) formed, suggesting that fungi were the dominant life form at this time, representing nearly 100% of the available fossil record for this period. However, the relative proportion of fungal spores relative to spores formed by algal species is difficult to assess, the spike did not appear worldwide, and in many places it did not fall on the Permian–Triassic boundary.

 

Sixty-five million years ago, immediately after the Cretaceous–Paleogene extinction event that famously killed off most dinosaurs, there was a dramatic increase in evidence of fungi; apparently the death of most plant and animal species led to a huge fungal bloom like "a massive compost heap".

 

Taxonomy

Although commonly included in botany curricula and textbooks, fungi are more closely related to animals than to plants and are placed with the animals in the monophyletic group of opisthokonts. Analyses using molecular phylogenetics support a monophyletic origin of fungi. The taxonomy of fungi is in a state of constant flux, especially due to research based on DNA comparisons. These current phylogenetic analyses often overturn classifications based on older and sometimes less discriminative methods based on morphological features and biological species concepts obtained from experimental matings.

 

There is no unique generally accepted system at the higher taxonomic levels and there are frequent name changes at every level, from species upwards. Efforts among researchers are now underway to establish and encourage usage of a unified and more consistent nomenclature. Until relatively recent (2012) changes to the International Code of Nomenclature for algae, fungi and plants, fungal species could also have multiple scientific names depending on their life cycle and mode (sexual or asexual) of reproduction. Web sites such as Index Fungorum and MycoBank are officially recognized nomenclatural repositories and list current names of fungal species (with cross-references to older synonyms).

 

The 2007 classification of Kingdom Fungi is the result of a large-scale collaborative research effort involving dozens of mycologists and other scientists working on fungal taxonomy. It recognizes seven phyla, two of which—the Ascomycota and the Basidiomycota—are contained within a branch representing subkingdom Dikarya, the most species rich and familiar group, including all the mushrooms, most food-spoilage molds, most plant pathogenic fungi, and the beer, wine, and bread yeasts. The accompanying cladogram depicts the major fungal taxa and their relationship to opisthokont and unikont organisms, based on the work of Philippe Silar, "The Mycota: A Comprehensive Treatise on Fungi as Experimental Systems for Basic and Applied Research" and Tedersoo et al. 2018. The lengths of the branches are not proportional to evolutionary distances.

 

The major phyla (sometimes called divisions) of fungi have been classified mainly on the basis of characteristics of their sexual reproductive structures. As of 2019, nine major lineages have been identified: Opisthosporidia, Chytridiomycota, Neocallimastigomycota, Blastocladiomycota, Zoopagomycotina, Mucoromycota, Glomeromycota, Ascomycota and Basidiomycota.

 

Phylogenetic analysis has demonstrated that the Microsporidia, unicellular parasites of animals and protists, are fairly recent and highly derived endobiotic fungi (living within the tissue of another species). Previously considered to be "primitive" protozoa, they are now thought to be either a basal branch of the Fungi, or a sister group–each other's closest evolutionary relative.

 

The Chytridiomycota are commonly known as chytrids. These fungi are distributed worldwide. Chytrids and their close relatives Neocallimastigomycota and Blastocladiomycota (below) are the only fungi with active motility, producing zoospores that are capable of active movement through aqueous phases with a single flagellum, leading early taxonomists to classify them as protists. Molecular phylogenies, inferred from rRNA sequences in ribosomes, suggest that the Chytrids are a basal group divergent from the other fungal phyla, consisting of four major clades with suggestive evidence for paraphyly or possibly polyphyly.

 

The Blastocladiomycota were previously considered a taxonomic clade within the Chytridiomycota. Molecular data and ultrastructural characteristics, however, place the Blastocladiomycota as a sister clade to the Zygomycota, Glomeromycota, and Dikarya (Ascomycota and Basidiomycota). The blastocladiomycetes are saprotrophs, feeding on decomposing organic matter, and they are parasites of all eukaryotic groups. Unlike their close relatives, the chytrids, most of which exhibit zygotic meiosis, the blastocladiomycetes undergo sporic meiosis.

 

The Neocallimastigomycota were earlier placed in the phylum Chytridiomycota. Members of this small phylum are anaerobic organisms, living in the digestive system of larger herbivorous mammals and in other terrestrial and aquatic environments enriched in cellulose (e.g., domestic waste landfill sites). They lack mitochondria but contain hydrogenosomes of mitochondrial origin. As in the related chrytrids, neocallimastigomycetes form zoospores that are posteriorly uniflagellate or polyflagellate.

 

Microscopic view of a layer of translucent grayish cells, some containing small dark-color spheres

Arbuscular mycorrhiza seen under microscope. Flax root cortical cells containing paired arbuscules.

Cross-section of a cup-shaped structure showing locations of developing meiotic asci (upper edge of cup, left side, arrows pointing to two gray cells containing four and two small circles), sterile hyphae (upper edge of cup, right side, arrows pointing to white cells with a single small circle in them), and mature asci (upper edge of cup, pointing to two gray cells with eight small circles in them)

Diagram of an apothecium (the typical cup-like reproductive structure of Ascomycetes) showing sterile tissues as well as developing and mature asci.

Members of the Glomeromycota form arbuscular mycorrhizae, a form of mutualist symbiosis wherein fungal hyphae invade plant root cells and both species benefit from the resulting increased supply of nutrients. All known Glomeromycota species reproduce asexually. The symbiotic association between the Glomeromycota and plants is ancient, with evidence dating to 400 million years ago. Formerly part of the Zygomycota (commonly known as 'sugar' and 'pin' molds), the Glomeromycota were elevated to phylum status in 2001 and now replace the older phylum Zygomycota. Fungi that were placed in the Zygomycota are now being reassigned to the Glomeromycota, or the subphyla incertae sedis Mucoromycotina, Kickxellomycotina, the Zoopagomycotina and the Entomophthoromycotina. Some well-known examples of fungi formerly in the Zygomycota include black bread mold (Rhizopus stolonifer), and Pilobolus species, capable of ejecting spores several meters through the air. Medically relevant genera include Mucor, Rhizomucor, and Rhizopus.

 

The Ascomycota, commonly known as sac fungi or ascomycetes, constitute the largest taxonomic group within the Eumycota. These fungi form meiotic spores called ascospores, which are enclosed in a special sac-like structure called an ascus. This phylum includes morels, a few mushrooms and truffles, unicellular yeasts (e.g., of the genera Saccharomyces, Kluyveromyces, Pichia, and Candida), and many filamentous fungi living as saprotrophs, parasites, and mutualistic symbionts (e.g. lichens). Prominent and important genera of filamentous ascomycetes include Aspergillus, Penicillium, Fusarium, and Claviceps. Many ascomycete species have only been observed undergoing asexual reproduction (called anamorphic species), but analysis of molecular data has often been able to identify their closest teleomorphs in the Ascomycota. Because the products of meiosis are retained within the sac-like ascus, ascomycetes have been used for elucidating principles of genetics and heredity (e.g., Neurospora crassa).

 

Members of the Basidiomycota, commonly known as the club fungi or basidiomycetes, produce meiospores called basidiospores on club-like stalks called basidia. Most common mushrooms belong to this group, as well as rust and smut fungi, which are major pathogens of grains. Other important basidiomycetes include the maize pathogen Ustilago maydis, human commensal species of the genus Malassezia, and the opportunistic human pathogen, Cryptococcus neoformans.

 

Fungus-like organisms

Because of similarities in morphology and lifestyle, the slime molds (mycetozoans, plasmodiophorids, acrasids, Fonticula and labyrinthulids, now in Amoebozoa, Rhizaria, Excavata, Opisthokonta and Stramenopiles, respectively), water molds (oomycetes) and hyphochytrids (both Stramenopiles) were formerly classified in the kingdom Fungi, in groups like Mastigomycotina, Gymnomycota and Phycomycetes. The slime molds were studied also as protozoans, leading to an ambiregnal, duplicated taxonomy.

 

Unlike true fungi, the cell walls of oomycetes contain cellulose and lack chitin. Hyphochytrids have both chitin and cellulose. Slime molds lack a cell wall during the assimilative phase (except labyrinthulids, which have a wall of scales), and take in nutrients by ingestion (phagocytosis, except labyrinthulids) rather than absorption (osmotrophy, as fungi, labyrinthulids, oomycetes and hyphochytrids). Neither water molds nor slime molds are closely related to the true fungi, and, therefore, taxonomists no longer group them in the kingdom Fungi. Nonetheless, studies of the oomycetes and myxomycetes are still often included in mycology textbooks and primary research literature.

 

The Eccrinales and Amoebidiales are opisthokont protists, previously thought to be zygomycete fungi. Other groups now in Opisthokonta (e.g., Corallochytrium, Ichthyosporea) were also at given time classified as fungi. The genus Blastocystis, now in Stramenopiles, was originally classified as a yeast. Ellobiopsis, now in Alveolata, was considered a chytrid. The bacteria were also included in fungi in some classifications, as the group Schizomycetes.

 

The Rozellida clade, including the "ex-chytrid" Rozella, is a genetically disparate group known mostly from environmental DNA sequences that is a sister group to fungi. Members of the group that have been isolated lack the chitinous cell wall that is characteristic of fungi. Alternatively, Rozella can be classified as a basal fungal group.

 

The nucleariids may be the next sister group to the eumycete clade, and as such could be included in an expanded fungal kingdom. Many Actinomycetales (Actinomycetota), a group with many filamentous bacteria, were also long believed to be fungi.

 

Ecology

Although often inconspicuous, fungi occur in every environment on Earth and play very important roles in most ecosystems. Along with bacteria, fungi are the major decomposers in most terrestrial (and some aquatic) ecosystems, and therefore play a critical role in biogeochemical cycles and in many food webs. As decomposers, they play an essential role in nutrient cycling, especially as saprotrophs and symbionts, degrading organic matter to inorganic molecules, which can then re-enter anabolic metabolic pathways in plants or other organisms.

 

Symbiosis

Many fungi have important symbiotic relationships with organisms from most if not all kingdoms. These interactions can be mutualistic or antagonistic in nature, or in the case of commensal fungi are of no apparent benefit or detriment to the host.

 

With plants

Mycorrhizal symbiosis between plants and fungi is one of the most well-known plant–fungus associations and is of significant importance for plant growth and persistence in many ecosystems; over 90% of all plant species engage in mycorrhizal relationships with fungi and are dependent upon this relationship for survival.

 

A microscopic view of blue-stained cells, some with dark wavy lines in them

The dark filaments are hyphae of the endophytic fungus Epichloë coenophiala in the intercellular spaces of tall fescue leaf sheath tissue

The mycorrhizal symbiosis is ancient, dating back to at least 400 million years. It often increases the plant's uptake of inorganic compounds, such as nitrate and phosphate from soils having low concentrations of these key plant nutrients. The fungal partners may also mediate plant-to-plant transfer of carbohydrates and other nutrients. Such mycorrhizal communities are called "common mycorrhizal networks". A special case of mycorrhiza is myco-heterotrophy, whereby the plant parasitizes the fungus, obtaining all of its nutrients from its fungal symbiont. Some fungal species inhabit the tissues inside roots, stems, and leaves, in which case they are called endophytes. Similar to mycorrhiza, endophytic colonization by fungi may benefit both symbionts; for example, endophytes of grasses impart to their host increased resistance to herbivores and other environmental stresses and receive food and shelter from the plant in return.

 

With algae and cyanobacteria

A green, leaf-like structure attached to a tree, with a pattern of ridges and depression on the bottom surface

The lichen Lobaria pulmonaria, a symbiosis of fungal, algal, and cyanobacterial species

Lichens are a symbiotic relationship between fungi and photosynthetic algae or cyanobacteria. The photosynthetic partner in the relationship is referred to in lichen terminology as a "photobiont". The fungal part of the relationship is composed mostly of various species of ascomycetes and a few basidiomycetes. Lichens occur in every ecosystem on all continents, play a key role in soil formation and the initiation of biological succession, and are prominent in some extreme environments, including polar, alpine, and semiarid desert regions. They are able to grow on inhospitable surfaces, including bare soil, rocks, tree bark, wood, shells, barnacles and leaves. As in mycorrhizas, the photobiont provides sugars and other carbohydrates via photosynthesis to the fungus, while the fungus provides minerals and water to the photobiont. The functions of both symbiotic organisms are so closely intertwined that they function almost as a single organism; in most cases the resulting organism differs greatly from the individual components. Lichenization is a common mode of nutrition for fungi; around 27% of known fungi—more than 19,400 species—are lichenized. Characteristics common to most lichens include obtaining organic carbon by photosynthesis, slow growth, small size, long life, long-lasting (seasonal) vegetative reproductive structures, mineral nutrition obtained largely from airborne sources, and greater tolerance of desiccation than most other photosynthetic organisms in the same habitat.

 

With insects

Many insects also engage in mutualistic relationships with fungi. Several groups of ants cultivate fungi in the order Chaetothyriales for several purposes: as a food source, as a structural component of their nests, and as a part of an ant/plant symbiosis in the domatia (tiny chambers in plants that house arthropods). Ambrosia beetles cultivate various species of fungi in the bark of trees that they infest. Likewise, females of several wood wasp species (genus Sirex) inject their eggs together with spores of the wood-rotting fungus Amylostereum areolatum into the sapwood of pine trees; the growth of the fungus provides ideal nutritional conditions for the development of the wasp larvae. At least one species of stingless bee has a relationship with a fungus in the genus Monascus, where the larvae consume and depend on fungus transferred from old to new nests. Termites on the African savannah are also known to cultivate fungi, and yeasts of the genera Candida and Lachancea inhabit the gut of a wide range of insects, including neuropterans, beetles, and cockroaches; it is not known whether these fungi benefit their hosts. Fungi growing in dead wood are essential for xylophagous insects (e.g. woodboring beetles). They deliver nutrients needed by xylophages to nutritionally scarce dead wood. Thanks to this nutritional enrichment the larvae of the woodboring insect is able to grow and develop to adulthood. The larvae of many families of fungicolous flies, particularly those within the superfamily Sciaroidea such as the Mycetophilidae and some Keroplatidae feed on fungal fruiting bodies and sterile mycorrhizae.

 

A thin brown stick positioned horizontally with roughly two dozen clustered orange-red leaves originating from a single point in the middle of the stick. These orange leaves are three to four times larger than the few other green leaves growing out of the stick, and are covered on the lower leaf surface with hundreds of tiny bumps. The background shows the green leaves and branches of neighboring shrubs.

The plant pathogen Puccinia magellanicum (calafate rust) causes the defect known as witch's broom, seen here on a barberry shrub in Chile.

 

Gram stain of Candida albicans from a vaginal swab from a woman with candidiasis, showing hyphae, and chlamydospores, which are 2–4 µm in diameter.

Many fungi are parasites on plants, animals (including humans), and other fungi. Serious pathogens of many cultivated plants causing extensive damage and losses to agriculture and forestry include the rice blast fungus Magnaporthe oryzae, tree pathogens such as Ophiostoma ulmi and Ophiostoma novo-ulmi causing Dutch elm disease, Cryphonectria parasitica responsible for chestnut blight, and Phymatotrichopsis omnivora causing Texas Root Rot, and plant pathogens in the genera Fusarium, Ustilago, Alternaria, and Cochliobolus. Some carnivorous fungi, like Paecilomyces lilacinus, are predators of nematodes, which they capture using an array of specialized structures such as constricting rings or adhesive nets. Many fungi that are plant pathogens, such as Magnaporthe oryzae, can switch from being biotrophic (parasitic on living plants) to being necrotrophic (feeding on the dead tissues of plants they have killed). This same principle is applied to fungi-feeding parasites, including Asterotremella albida, which feeds on the fruit bodies of other fungi both while they are living and after they are dead.

 

Some fungi can cause serious diseases in humans, several of which may be fatal if untreated. These include aspergillosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mycetomas, and paracoccidioidomycosis. Furthermore, persons with immuno-deficiencies are particularly susceptible to disease by genera such as Aspergillus, Candida, Cryptoccocus, Histoplasma, and Pneumocystis. Other fungi can attack eyes, nails, hair, and especially skin, the so-called dermatophytic and keratinophilic fungi, and cause local infections such as ringworm and athlete's foot. Fungal spores are also a cause of allergies, and fungi from different taxonomic groups can evoke allergic reactions.

 

As targets of mycoparasites

Organisms that parasitize fungi are known as mycoparasitic organisms. About 300 species of fungi and fungus-like organisms, belonging to 13 classes and 113 genera, are used as biocontrol agents against plant fungal diseases. Fungi can also act as mycoparasites or antagonists of other fungi, such as Hypomyces chrysospermus, which grows on bolete mushrooms. Fungi can also become the target of infection by mycoviruses.

 

Communication

Main article: Mycorrhizal networks

There appears to be electrical communication between fungi in word-like components according to spiking characteristics.

 

Possible impact on climate

According to a study published in the academic journal Current Biology, fungi can soak from the atmosphere around 36% of global fossil fuel greenhouse gas emissions.

 

Mycotoxins

(6aR,9R)-N-((2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-2H-oxazolo[3,2-a] pyrrolo[2,1-c]pyrazin-2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg] quinoline-9-carboxamide

Ergotamine, a major mycotoxin produced by Claviceps species, which if ingested can cause gangrene, convulsions, and hallucinations

Many fungi produce biologically active compounds, several of which are toxic to animals or plants and are therefore called mycotoxins. Of particular relevance to humans are mycotoxins produced by molds causing food spoilage, and poisonous mushrooms (see above). Particularly infamous are the lethal amatoxins in some Amanita mushrooms, and ergot alkaloids, which have a long history of causing serious epidemics of ergotism (St Anthony's Fire) in people consuming rye or related cereals contaminated with sclerotia of the ergot fungus, Claviceps purpurea. Other notable mycotoxins include the aflatoxins, which are insidious liver toxins and highly carcinogenic metabolites produced by certain Aspergillus species often growing in or on grains and nuts consumed by humans, ochratoxins, patulin, and trichothecenes (e.g., T-2 mycotoxin) and fumonisins, which have significant impact on human food supplies or animal livestock.

 

Mycotoxins are secondary metabolites (or natural products), and research has established the existence of biochemical pathways solely for the purpose of producing mycotoxins and other natural products in fungi. Mycotoxins may provide fitness benefits in terms of physiological adaptation, competition with other microbes and fungi, and protection from consumption (fungivory). Many fungal secondary metabolites (or derivatives) are used medically, as described under Human use below.

 

Pathogenic mechanisms

Ustilago maydis is a pathogenic plant fungus that causes smut disease in maize and teosinte. Plants have evolved efficient defense systems against pathogenic microbes such as U. maydis. A rapid defense reaction after pathogen attack is the oxidative burst where the plant produces reactive oxygen species at the site of the attempted invasion. U. maydis can respond to the oxidative burst with an oxidative stress response, regulated by the gene YAP1. The response protects U. maydis from the host defense, and is necessary for the pathogen's virulence. Furthermore, U. maydis has a well-established recombinational DNA repair system which acts during mitosis and meiosis. The system may assist the pathogen in surviving DNA damage arising from the host plant's oxidative defensive response to infection.

 

Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. C. neoformans usually infects the lungs, where it is phagocytosed by alveolar macrophages. Some C. neoformans can survive inside macrophages, which appears to be the basis for latency, disseminated disease, and resistance to antifungal agents. One mechanism by which C. neoformans survives the hostile macrophage environment is by up-regulating the expression of genes involved in the oxidative stress response. Another mechanism involves meiosis. The majority of C. neoformans are mating "type a". Filaments of mating "type a" ordinarily have haploid nuclei, but they can become diploid (perhaps by endoduplication or by stimulated nuclear fusion) to form blastospores. The diploid nuclei of blastospores can undergo meiosis, including recombination, to form haploid basidiospores that can be dispersed. This process is referred to as monokaryotic fruiting. This process requires a gene called DMC1, which is a conserved homologue of genes recA in bacteria and RAD51 in eukaryotes, that mediates homologous chromosome pairing during meiosis and repair of DNA double-strand breaks. Thus, C. neoformans can undergo a meiosis, monokaryotic fruiting, that promotes recombinational repair in the oxidative, DNA damaging environment of the host macrophage, and the repair capability may contribute to its virulence.

 

Human use

See also: Human interactions with fungi

Microscopic view of five spherical structures; one of the spheres is considerably smaller than the rest and attached to one of the larger spheres

Saccharomyces cerevisiae cells shown with DIC microscopy

The human use of fungi for food preparation or preservation and other purposes is extensive and has a long history. Mushroom farming and mushroom gathering are large industries in many countries. The study of the historical uses and sociological impact of fungi is known as ethnomycology. Because of the capacity of this group to produce an enormous range of natural products with antimicrobial or other biological activities, many species have long been used or are being developed for industrial production of antibiotics, vitamins, and anti-cancer and cholesterol-lowering drugs. Methods have been developed for genetic engineering of fungi, enabling metabolic engineering of fungal species. For example, genetic modification of yeast species—which are easy to grow at fast rates in large fermentation vessels—has opened up ways of pharmaceutical production that are potentially more efficient than production by the original source organisms. Fungi-based industries are sometimes considered to be a major part of a growing bioeconomy, with applications under research and development including use for textiles, meat substitution and general fungal biotechnology.

 

Therapeutic uses

Modern chemotherapeutics

Many species produce metabolites that are major sources of pharmacologically active drugs.

 

Antibiotics

Particularly important are the antibiotics, including the penicillins, a structurally related group of β-lactam antibiotics that are synthesized from small peptides. Although naturally occurring penicillins such as penicillin G (produced by Penicillium chrysogenum) have a relatively narrow spectrum of biological activity, a wide range of other penicillins can be produced by chemical modification of the natural penicillins. Modern penicillins are semisynthetic compounds, obtained initially from fermentation cultures, but then structurally altered for specific desirable properties. Other antibiotics produced by fungi include: ciclosporin, commonly used as an immunosuppressant during transplant surgery; and fusidic acid, used to help control infection from methicillin-resistant Staphylococcus aureus bacteria. Widespread use of antibiotics for the treatment of bacterial diseases, such as tuberculosis, syphilis, leprosy, and others began in the early 20th century and continues to date. In nature, antibiotics of fungal or bacterial origin appear to play a dual role: at high concentrations they act as chemical defense against competition with other microorganisms in species-rich environments, such as the rhizosphere, and at low concentrations as quorum-sensing molecules for intra- or interspecies signaling.

 

Other

Other drugs produced by fungi include griseofulvin isolated from Penicillium griseofulvum, used to treat fungal infections, and statins (HMG-CoA reductase inhibitors), used to inhibit cholesterol synthesis. Examples of statins found in fungi include mevastatin from Penicillium citrinum and lovastatin from Aspergillus terreus and the oyster mushroom. Psilocybin from fungi is investigated for therapeutic use and appears to cause global increases in brain network integration. Fungi produce compounds that inhibit viruses and cancer cells. Specific metabolites, such as polysaccharide-K, ergotamine, and β-lactam antibiotics, are routinely used in clinical medicine. The shiitake mushroom is a source of lentinan, a clinical drug approved for use in cancer treatments in several countries, including Japan. In Europe and Japan, polysaccharide-K (brand name Krestin), a chemical derived from Trametes versicolor, is an approved adjuvant for cancer therapy.

 

Traditional medicine

Upper surface view of a kidney-shaped fungus, brownish-red with a lighter yellow-brown margin, and a somewhat varnished or shiny appearance

Two dried yellow-orange caterpillars, one with a curly grayish fungus growing out of one of its ends. The grayish fungus is roughly equal to or slightly greater in length than the caterpillar, and tapers in thickness to a narrow end.

The fungi Ganoderma lucidum (left) and Ophiocordyceps sinensis (right) are used in traditional medicine practices

Certain mushrooms are used as supposed therapeutics in folk medicine practices, such as traditional Chinese medicine. Mushrooms with a history of such use include Agaricus subrufescens, Ganoderma lucidum, and Ophiocordyceps sinensis.

 

Cultured foods

Baker's yeast or Saccharomyces cerevisiae, a unicellular fungus, is used to make bread and other wheat-based products, such as pizza dough and dumplings. Yeast species of the genus Saccharomyces are also used to produce alcoholic beverages through fermentation. Shoyu koji mold (Aspergillus oryzae) is an essential ingredient in brewing Shoyu (soy sauce) and sake, and the preparation of miso while Rhizopus species are used for making tempeh. Several of these fungi are domesticated species that were bred or selected according to their capacity to ferment food without producing harmful mycotoxins (see below), which are produced by very closely related Aspergilli. Quorn, a meat substitute, is made from Fusarium venenatum.

Curled up young leaves of Raukaua simplex. Insect feeding or pathogen?

I was invited to spend two days at Europe’s most comprehensive IoT Event. This leading forum focused on case studies that show today’s Industry and Enterprises leveraging IoT technologies to transform their business through creating value and efficiencies.

 

The Internet of things (stylised Internet of Things or IoT) is the internetworking of physical devices, vehicles (also referred to as "connected devices" and "smart devices"), buildings and other items—embedded with electronics, software, sensors, actuators, and network connectivity that enable these objects to collect and exchange data.

 

"Things," in the IoT sense, can refer to a wide variety of devices such as heart monitoring implants, biochip transponders on farm animals, electric clams in coastal waters,[16] automobiles with built-in sensors, DNA analysis devices for environmental/food/pathogen monitoring or field operation devices that assist firefighters in search and rescue operations.[18] Legal scholars suggest to look at "Things" as an "inextricable mixture of hardware, software, data and service". These devices collect useful data with the help of various existing technologies and then autonomously flow the data between other devices. Current market examples include home automation (also known as smart home devices) such as the control and automation of lighting, heating (like smart thermostat), ventilation, air conditioning (HVAC) systems, and appliances such as washer/dryers, robotic vacuums, air purifiers, ovens or refrigerators/freezers that use Wi-Fi for remote monitoring.

Pathogen Common name: Sooty Bark Mold

Pathogen Scientific name: Arthrobotryum spongiosum

Host Scientific Name: Calocedrus decurrens

Forest Type: Mixed Coniferous

Collected in Burnt Ranch, Trinity County, Ca. at

approximately 1000’ elevation.

 

This nest was in Saguaro National Park (east) Arizona.

Studies show grooming may integrate chemical cues used for recognizing nest-mates as well as removing parasites or pathogens.

 

This was shot with a Canon EF 100mm f2.8L Macro Lens mounted on a Panasonic GH3 Micro Four Thirds camera using a Metabones Smart Adapter.

by David T. Hill : Updated March 9, 2020 Anno Domini

 

"Copper is great at killing superbugs – so why don’t hospitals use it?

 

Copper and its alloys exhibit impressive antibacterial, anti-fungal and antiviral properties. Copper has been exploited for health purposes since ancient times. Egyptian and Babylonian soldiers would sharpen their bronze swords (an alloy of copper and tin) after a battle, and place the filings in their wounds to reduce infection and speed healing.

 

The process involves the release of copper ions (electrically charged particles) when microbes, transferred by touching, sneezing or vomiting, land on the copper surface. The ions prevent cell respiration, punch holes in the bacterial cell membrane or disrupt the viral coat, and destroy the DNA and RNA inside.

 

This latter property is important as it means that no mutation can occur – preventing the microbe from developing resistance to copper. Copper alloys kill superbugs, including MRSA and those from the notorious ESKAPE group of pathogens – the leading cause of hospital-acquired infections."

 

theconversation.com/copper-is-great-at-killing-superbugs-...

 

It has been recorded that both Kids and Women (and probably African Americans) have more immunity to Coronavirus then adult Men and the probable reason is that these groups have higher Copper content in their systems. See quotes below.

 

Copper Tincture :

 

"Put some copper pennies into vinegar overnight. The vinegar may turn pale blue - that is the cuprous ion. Add a drop of that to your coffee, tea or food for copper. Good idea, but don't overdo it. Copper coating on pennies is fine since it is still copper. You can buy copper supplements but I'd rather do it this way."

 

lunaticoutpost.com/thread-167147-post-3115235.html?fbclid...

 

You can use this for ingestion and you could also make a bigger batch and use it for cleaning - dampen a rag and wipe down all surfaces - tables, counters, door handles, etc. You could even take a sponge bath with it. Mix it with vaseline and dab it in your nostrils and every time you breathe in you will be putting copper ions into your lungs but this should probably only be done if you have actually contracted the virus.

 

The Masks are virtually useless (because they don't make an air tight seal so its a waste of time shaving your beards boys) but if you soak one in this solution it will kill the virus (making masks reusable) and wear it damp every time you breathe in you will be breathing in Copper Ions which will kill the Virus in your lungs as well as making it into your Blood Stream. But you will need to monitor for Copper Toxicity (Headaches, acne, greenish complexion, etc., see url below).

 

You could pour this solution into a Humidifier and, in theory, Ionize an entire room and turn it into an impromptu clinic if you needed to but, again, this should be only if you have contracted the virus.

 

There is no proof that Colloidal Silver or Vitamin C kills viruses (see quotes below) and, in fact, the Aids Community tried both and neither one worked so they discarded that practice so you probably don't want to waste your time with Silver or Vitamins to stop a Weaponized Virus (Antiviral Research, Vol. 16, April 2020, Article : The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade) which is probably Airborne like Influenza (New England Journal of Medicine, Feb. 19, 2020 SARS-CoV-2, Article : Viral Load in Upper Respiratory Specimens of Infected Patients). Copper Ions, however, have been proven to kill both the HIV Virus and Coronavirus (see quote below).

 

Some multivitamins have copper in them. You can make some impromptu 'silverware' so you ingest particulates of copper on a regular basis so it gets in your blood. You can make rings out of copper grounding wire and wear them on you hands and then everything you touch will have copper particles on them. You can even carry a penny in you mouth off and on but make sure you use an older penny cause the recent ones are only copper coated.

 

"You can buy colloidal copper in liquid form (gold too)."

 

lunaticoutpost.com/thread-167147-post-3115387.html?fbclid...

 

You can ask at any pharmacy like Walmart or any good Vitamin Store and they should be able to order liquid colloidal copper for you if they don't already carry it in stock and it should have the normal dosage suggestions on the bottle.

 

What is Colloidal Copper :

 

www.healthline.com/health/colloidal-copper

 

Colloidal Silver :

 

"Proponents of colloidal silver claim that it can have antiviral effects in your body. Some studies have suggested that different types of silver nanoparticles may help kill viral compounds. However, the amount of nanoparticles in a colloid solution can vary and a recent study found colloidal silver to be ineffective at killing viruses, even in test-tube conditions."

 

www.healthline.com/nutrition/colloidal-silver?fbclid=IwAR...

 

Vitamin C :

 

"Several years ago there was much interest in high-dose Vitamin C as an HIV treatment. By the end of 1987 this interest had greatly diminished, although some people continue to use the treatment today. One reason we have been skeptical of Vitamin C is that if the treatment had worked well, it seems unlikely that the community would have stopped using it."

 

www.aids.org/2010/10/vitamin-c-laboratory-tests-indicate-...

 

HIV :

 

"Incorporation of copper alloy surfaces in conjunction with effective cleaning regimens and good clinical practice could help to control transmission of respiratory coronaviruses, including MERS and SARS.

 

Copper alloys have demonstrated excellent antibacterial and antifungal activity against a range of pathogens in laboratory studies (14,–19). Copper ion release has been found to be essential to maintaining efficacy, but the mechanism of action is variable (20, 21). A reduction in microbial bioburden and acquisition of nosocomial infection has now been observed in clinical trials of incorporation of copper alloy surfaces in health care facilities (22,–25).

 

Rapid inactivation of human coronavirus occurs on brass and copper nickel surfaces at room temperature (21°C).Inactivation of coronavirus on copper and copper alloy surfaces results in fragmentation of the viral genome, ensuring that inactivation is irreversible.

 

Copper ions have been shown to directly inhibit proteases by reacting with surface cysteine and to inflict damage to the viral genome in HIV and herpes simplex virus (40, 41).

 

The mechanism of bacterial death on copper surfaces is complex, involving not only direct action of copper ion on multiple targets but also the generation of destructive oxygen radicals, resulting in “metabolic suicide” (20). This was not observed for norovirus destruction on copper, presumably because of the lack of respiratory machinery (26). However, it appears that superoxide and hydroxyl radical generation may be important in the inactivation of coronaviruses on copper alloys but that inactivation on 100% copper surfaces is primarily due to the direct effect of copper ions.

 

In this study, we observed rapid damage, including clumping, breakage, membrane damage, and loss of surface spikes, to the coronavirus particles following exposure to copper, and some particles appeared smaller and seemed to have lost rigidity, folding up on themselves. These changes were not observed with virus recovered from stainless steel surfaces.

 

There is now a large body of evidence from laboratory studies and small clinical trials to suggest that incorporation of copper surfaces could play a significant role in reducing infection transmission from contaminated surfaces."

 

www.ncbi.nlm.nih.gov/pmc/articles/PMC4659470/

 

Plasma Copper in Human Subjects

 

"Plasma copper was not correlated with age among control subjects or AD patients. Plasma and cerebrospinal fluid copper were not correlated in any group.

 

Plasma copper is increased in human female (1008 ± 51) compared to male (836 ± 41) control subjects (P = 0.01) when all age groups were combined. When the control subjects were divided by age group, trends to higher plasma copper in females were appreciated in the middle-aged and old control subjects, but not the young subjects."

 

www.ncbi.nlm.nih.gov/pmc/articles/PMC3199105/

 

"Copper levels in plasma and erythrocytes in healthy Japanese children and adults.

 

This study showed differences in plasma and erythrocyte copper concentrations in children and adults. All determinations were performed with a flameless atomic absorption spectrophotometer. The mean plasma copper level at 1 month of age was significantly lower than in adults. After 1 month of age the mean concentration in plasma increased to its peak value at 2 to 5 yr of age, then decreased gradually with age. At 7 months to 10 yr of age, the copper levels in plasma were significantly higher than in adults. The erythrocyte copper levels at 1 month to 1 yr of age were significantly higher than in adults. The copper content of erythrocytes was highest at 2 to 6 months of age and then decreased gradually. The copper concentration of erythrocytes may reflect more accurately liver and total body copper levels than does the plasma copper level. There is less possibility of copper contamination in erythrocytes than in hair. Therefore, the measurement of erythrocyte copper concentration may well be a helpful index of the total copper status."

 

www.ncbi.nlm.nih.gov/pubmed/7064868

  

Copper Toxicity Symptoms :

 

www.holistic-back-relief.com/images/x7-signs-of-Copper-to...

 

Original Post :

 

theoferrum.activeboard.com/t66302031/copper-ions-the-silv...

Order: Ascomycota

Family: Rhytismataceae

Genus: Rhytisma

 

***

 

English: Tar spot

 

Deutsch: Ahorn-Runzelschorf

 

Magyar: Juhar pecsétfoltosság

 

Français: Tache goudronneuse

 

Español: Mancha de alquitrán del arce

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

——————————————————————————

(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

  

-------------------------------------------------- ---------------------

    

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

A fungus (pl.: fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the traditional eukaryotic kingdoms, along with Animalia, Plantae and either Protista or Protozoa and Chromista.

 

A characteristic that places fungi in a different kingdom from plants, bacteria, and some protists is chitin in their cell walls. Fungi, like animals, are heterotrophs; they acquire their food by absorbing dissolved molecules, typically by secreting digestive enzymes into their environment. Fungi do not photosynthesize. Growth is their means of mobility, except for spores (a few of which are flagellated), which may travel through the air or water. Fungi are the principal decomposers in ecological systems. These and other differences place fungi in a single group of related organisms, named the Eumycota (true fungi or Eumycetes), that share a common ancestor (i.e. they form a monophyletic group), an interpretation that is also strongly supported by molecular phylogenetics. This fungal group is distinct from the structurally similar myxomycetes (slime molds) and oomycetes (water molds). The discipline of biology devoted to the study of fungi is known as mycology (from the Greek μύκης mykes, mushroom). In the past mycology was regarded as a branch of botany, although it is now known that fungi are genetically more closely related to animals than to plants.

 

Abundant worldwide, most fungi are inconspicuous because of the small size of their structures, and their cryptic lifestyles in soil or on dead matter. Fungi include symbionts of plants, animals, or other fungi and also parasites. They may become noticeable when fruiting, either as mushrooms or as molds. Fungi perform an essential role in the decomposition of organic matter and have fundamental roles in nutrient cycling and exchange in the environment. They have long been used as a direct source of human food, in the form of mushrooms and truffles; as a leavening agent for bread; and in the fermentation of various food products, such as wine, beer, and soy sauce. Since the 1940s, fungi have been used for the production of antibiotics, and, more recently, various enzymes produced by fungi are used industrially and in detergents. Fungi are also used as biological pesticides to control weeds, plant diseases, and insect pests. Many species produce bioactive compounds called mycotoxins, such as alkaloids and polyketides, that are toxic to animals, including humans. The fruiting structures of a few species contain psychotropic compounds and are consumed recreationally or in traditional spiritual ceremonies. Fungi can break down manufactured materials and buildings, and become significant pathogens of humans and other animals. Losses of crops due to fungal diseases (e.g., rice blast disease) or food spoilage can have a large impact on human food supplies and local economies.

 

The fungus kingdom encompasses an enormous diversity of taxa with varied ecologies, life cycle strategies, and morphologies ranging from unicellular aquatic chytrids to large mushrooms. However, little is known of the true biodiversity of the fungus kingdom, which has been estimated at 2.2 million to 3.8 million species. Of these, only about 148,000 have been described, with over 8,000 species known to be detrimental to plants and at least 300 that can be pathogenic to humans. Ever since the pioneering 18th and 19th century taxonomical works of Carl Linnaeus, Christiaan Hendrik Persoon, and Elias Magnus Fries, fungi have been classified according to their morphology (e.g., characteristics such as spore color or microscopic features) or physiology. Advances in molecular genetics have opened the way for DNA analysis to be incorporated into taxonomy, which has sometimes challenged the historical groupings based on morphology and other traits. Phylogenetic studies published in the first decade of the 21st century have helped reshape the classification within the fungi kingdom, which is divided into one subkingdom, seven phyla, and ten subphyla.

 

Etymology

The English word fungus is directly adopted from the Latin fungus (mushroom), used in the writings of Horace and Pliny. This in turn is derived from the Greek word sphongos (σφόγγος 'sponge'), which refers to the macroscopic structures and morphology of mushrooms and molds; the root is also used in other languages, such as the German Schwamm ('sponge') and Schimmel ('mold').

 

The word mycology is derived from the Greek mykes (μύκης 'mushroom') and logos (λόγος 'discourse'). It denotes the scientific study of fungi. The Latin adjectival form of "mycology" (mycologicæ) appeared as early as 1796 in a book on the subject by Christiaan Hendrik Persoon. The word appeared in English as early as 1824 in a book by Robert Kaye Greville. In 1836 the English naturalist Miles Joseph Berkeley's publication The English Flora of Sir James Edward Smith, Vol. 5. also refers to mycology as the study of fungi.

 

A group of all the fungi present in a particular region is known as mycobiota (plural noun, no singular). The term mycota is often used for this purpose, but many authors use it as a synonym of Fungi. The word funga has been proposed as a less ambiguous term morphologically similar to fauna and flora. The Species Survival Commission (SSC) of the International Union for Conservation of Nature (IUCN) in August 2021 asked that the phrase fauna and flora be replaced by fauna, flora, and funga.

 

Characteristics

 

Fungal hyphae cells

Hyphal wall

Septum

Mitochondrion

Vacuole

Ergosterol crystal

Ribosome

Nucleus

Endoplasmic reticulum

Lipid body

Plasma membrane

Spitzenkörper

Golgi apparatus

 

Fungal cell cycle showing Dikaryons typical of Higher Fungi

Before the introduction of molecular methods for phylogenetic analysis, taxonomists considered fungi to be members of the plant kingdom because of similarities in lifestyle: both fungi and plants are mainly immobile, and have similarities in general morphology and growth habitat. Although inaccurate, the common misconception that fungi are plants persists among the general public due to their historical classification, as well as several similarities. Like plants, fungi often grow in soil and, in the case of mushrooms, form conspicuous fruit bodies, which sometimes resemble plants such as mosses. The fungi are now considered a separate kingdom, distinct from both plants and animals, from which they appear to have diverged around one billion years ago (around the start of the Neoproterozoic Era). Some morphological, biochemical, and genetic features are shared with other organisms, while others are unique to the fungi, clearly separating them from the other kingdoms:

 

With other eukaryotes: Fungal cells contain membrane-bound nuclei with chromosomes that contain DNA with noncoding regions called introns and coding regions called exons. Fungi have membrane-bound cytoplasmic organelles such as mitochondria, sterol-containing membranes, and ribosomes of the 80S type. They have a characteristic range of soluble carbohydrates and storage compounds, including sugar alcohols (e.g., mannitol), disaccharides, (e.g., trehalose), and polysaccharides (e.g., glycogen, which is also found in animals).

With animals: Fungi lack chloroplasts and are heterotrophic organisms and so require preformed organic compounds as energy sources.

With plants: Fungi have a cell wall and vacuoles. They reproduce by both sexual and asexual means, and like basal plant groups (such as ferns and mosses) produce spores. Similar to mosses and algae, fungi typically have haploid nuclei.

With euglenoids and bacteria: Higher fungi, euglenoids, and some bacteria produce the amino acid L-lysine in specific biosynthesis steps, called the α-aminoadipate pathway.

The cells of most fungi grow as tubular, elongated, and thread-like (filamentous) structures called hyphae, which may contain multiple nuclei and extend by growing at their tips. Each tip contains a set of aggregated vesicles—cellular structures consisting of proteins, lipids, and other organic molecules—called the Spitzenkörper. Both fungi and oomycetes grow as filamentous hyphal cells. In contrast, similar-looking organisms, such as filamentous green algae, grow by repeated cell division within a chain of cells. There are also single-celled fungi (yeasts) that do not form hyphae, and some fungi have both hyphal and yeast forms.

In common with some plant and animal species, more than one hundred fungal species display bioluminescence.

Unique features:

 

Some species grow as unicellular yeasts that reproduce by budding or fission. Dimorphic fungi can switch between a yeast phase and a hyphal phase in response to environmental conditions.

The fungal cell wall is made of a chitin-glucan complex; while glucans are also found in plants and chitin in the exoskeleton of arthropods, fungi are the only organisms that combine these two structural molecules in their cell wall. Unlike those of plants and oomycetes, fungal cell walls do not contain cellulose.

A whitish fan or funnel-shaped mushroom growing at the base of a tree.

Omphalotus nidiformis, a bioluminescent mushroom

Most fungi lack an efficient system for the long-distance transport of water and nutrients, such as the xylem and phloem in many plants. To overcome this limitation, some fungi, such as Armillaria, form rhizomorphs, which resemble and perform functions similar to the roots of plants. As eukaryotes, fungi possess a biosynthetic pathway for producing terpenes that uses mevalonic acid and pyrophosphate as chemical building blocks. Plants and some other organisms have an additional terpene biosynthesis pathway in their chloroplasts, a structure that fungi and animals do not have. Fungi produce several secondary metabolites that are similar or identical in structure to those made by plants. Many of the plant and fungal enzymes that make these compounds differ from each other in sequence and other characteristics, which indicates separate origins and convergent evolution of these enzymes in the fungi and plants.

 

Diversity

Fungi have a worldwide distribution, and grow in a wide range of habitats, including extreme environments such as deserts or areas with high salt concentrations or ionizing radiation, as well as in deep sea sediments. Some can survive the intense UV and cosmic radiation encountered during space travel. Most grow in terrestrial environments, though several species live partly or solely in aquatic habitats, such as the chytrid fungi Batrachochytrium dendrobatidis and B. salamandrivorans, parasites that have been responsible for a worldwide decline in amphibian populations. These organisms spend part of their life cycle as a motile zoospore, enabling them to propel itself through water and enter their amphibian host. Other examples of aquatic fungi include those living in hydrothermal areas of the ocean.

 

As of 2020, around 148,000 species of fungi have been described by taxonomists, but the global biodiversity of the fungus kingdom is not fully understood. A 2017 estimate suggests there may be between 2.2 and 3.8 million species The number of new fungi species discovered yearly has increased from 1,000 to 1,500 per year about 10 years ago, to about 2000 with a peak of more than 2,500 species in 2016. In the year 2019, 1882 new species of fungi were described, and it was estimated that more than 90% of fungi remain unknown The following year, 2905 new species were described—the highest annual record of new fungus names. In mycology, species have historically been distinguished by a variety of methods and concepts. Classification based on morphological characteristics, such as the size and shape of spores or fruiting structures, has traditionally dominated fungal taxonomy. Species may also be distinguished by their biochemical and physiological characteristics, such as their ability to metabolize certain biochemicals, or their reaction to chemical tests. The biological species concept discriminates species based on their ability to mate. The application of molecular tools, such as DNA sequencing and phylogenetic analysis, to study diversity has greatly enhanced the resolution and added robustness to estimates of genetic diversity within various taxonomic groups.

 

Mycology

Mycology is the branch of biology concerned with the systematic study of fungi, including their genetic and biochemical properties, their taxonomy, and their use to humans as a source of medicine, food, and psychotropic substances consumed for religious purposes, as well as their dangers, such as poisoning or infection. The field of phytopathology, the study of plant diseases, is closely related because many plant pathogens are fungi.

 

The use of fungi by humans dates back to prehistory; Ötzi the Iceman, a well-preserved mummy of a 5,300-year-old Neolithic man found frozen in the Austrian Alps, carried two species of polypore mushrooms that may have been used as tinder (Fomes fomentarius), or for medicinal purposes (Piptoporus betulinus). Ancient peoples have used fungi as food sources—often unknowingly—for millennia, in the preparation of leavened bread and fermented juices. Some of the oldest written records contain references to the destruction of crops that were probably caused by pathogenic fungi.

 

History

Mycology became a systematic science after the development of the microscope in the 17th century. Although fungal spores were first observed by Giambattista della Porta in 1588, the seminal work in the development of mycology is considered to be the publication of Pier Antonio Micheli's 1729 work Nova plantarum genera. Micheli not only observed spores but also showed that, under the proper conditions, they could be induced into growing into the same species of fungi from which they originated. Extending the use of the binomial system of nomenclature introduced by Carl Linnaeus in his Species plantarum (1753), the Dutch Christiaan Hendrik Persoon (1761–1836) established the first classification of mushrooms with such skill as to be considered a founder of modern mycology. Later, Elias Magnus Fries (1794–1878) further elaborated the classification of fungi, using spore color and microscopic characteristics, methods still used by taxonomists today. Other notable early contributors to mycology in the 17th–19th and early 20th centuries include Miles Joseph Berkeley, August Carl Joseph Corda, Anton de Bary, the brothers Louis René and Charles Tulasne, Arthur H. R. Buller, Curtis G. Lloyd, and Pier Andrea Saccardo. In the 20th and 21st centuries, advances in biochemistry, genetics, molecular biology, biotechnology, DNA sequencing and phylogenetic analysis has provided new insights into fungal relationships and biodiversity, and has challenged traditional morphology-based groupings in fungal taxonomy.

 

Morphology

Microscopic structures

Monochrome micrograph showing Penicillium hyphae as long, transparent, tube-like structures a few micrometres across. Conidiophores branch out laterally from the hyphae, terminating in bundles of phialides on which spherical condidiophores are arranged like beads on a string. Septa are faintly visible as dark lines crossing the hyphae.

An environmental isolate of Penicillium

Hypha

Conidiophore

Phialide

Conidia

Septa

Most fungi grow as hyphae, which are cylindrical, thread-like structures 2–10 µm in diameter and up to several centimeters in length. Hyphae grow at their tips (apices); new hyphae are typically formed by emergence of new tips along existing hyphae by a process called branching, or occasionally growing hyphal tips fork, giving rise to two parallel-growing hyphae. Hyphae also sometimes fuse when they come into contact, a process called hyphal fusion (or anastomosis). These growth processes lead to the development of a mycelium, an interconnected network of hyphae. Hyphae can be either septate or coenocytic. Septate hyphae are divided into compartments separated by cross walls (internal cell walls, called septa, that are formed at right angles to the cell wall giving the hypha its shape), with each compartment containing one or more nuclei; coenocytic hyphae are not compartmentalized. Septa have pores that allow cytoplasm, organelles, and sometimes nuclei to pass through; an example is the dolipore septum in fungi of the phylum Basidiomycota. Coenocytic hyphae are in essence multinucleate supercells.

 

Many species have developed specialized hyphal structures for nutrient uptake from living hosts; examples include haustoria in plant-parasitic species of most fungal phyla,[63] and arbuscules of several mycorrhizal fungi, which penetrate into the host cells to consume nutrients.

 

Although fungi are opisthokonts—a grouping of evolutionarily related organisms broadly characterized by a single posterior flagellum—all phyla except for the chytrids have lost their posterior flagella. Fungi are unusual among the eukaryotes in having a cell wall that, in addition to glucans (e.g., β-1,3-glucan) and other typical components, also contains the biopolymer chitin.

 

Macroscopic structures

Fungal mycelia can become visible to the naked eye, for example, on various surfaces and substrates, such as damp walls and spoiled food, where they are commonly called molds. Mycelia grown on solid agar media in laboratory petri dishes are usually referred to as colonies. These colonies can exhibit growth shapes and colors (due to spores or pigmentation) that can be used as diagnostic features in the identification of species or groups. Some individual fungal colonies can reach extraordinary dimensions and ages as in the case of a clonal colony of Armillaria solidipes, which extends over an area of more than 900 ha (3.5 square miles), with an estimated age of nearly 9,000 years.

 

The apothecium—a specialized structure important in sexual reproduction in the ascomycetes—is a cup-shaped fruit body that is often macroscopic and holds the hymenium, a layer of tissue containing the spore-bearing cells. The fruit bodies of the basidiomycetes (basidiocarps) and some ascomycetes can sometimes grow very large, and many are well known as mushrooms.

 

Growth and physiology

Time-lapse photography sequence of a peach becoming progressively discolored and disfigured

Mold growth covering a decaying peach. The frames were taken approximately 12 hours apart over a period of six days.

The growth of fungi as hyphae on or in solid substrates or as single cells in aquatic environments is adapted for the efficient extraction of nutrients, because these growth forms have high surface area to volume ratios. Hyphae are specifically adapted for growth on solid surfaces, and to invade substrates and tissues. They can exert large penetrative mechanical forces; for example, many plant pathogens, including Magnaporthe grisea, form a structure called an appressorium that evolved to puncture plant tissues.[71] The pressure generated by the appressorium, directed against the plant epidermis, can exceed 8 megapascals (1,200 psi).[71] The filamentous fungus Paecilomyces lilacinus uses a similar structure to penetrate the eggs of nematodes.

 

The mechanical pressure exerted by the appressorium is generated from physiological processes that increase intracellular turgor by producing osmolytes such as glycerol. Adaptations such as these are complemented by hydrolytic enzymes secreted into the environment to digest large organic molecules—such as polysaccharides, proteins, and lipids—into smaller molecules that may then be absorbed as nutrients. The vast majority of filamentous fungi grow in a polar fashion (extending in one direction) by elongation at the tip (apex) of the hypha. Other forms of fungal growth include intercalary extension (longitudinal expansion of hyphal compartments that are below the apex) as in the case of some endophytic fungi, or growth by volume expansion during the development of mushroom stipes and other large organs. Growth of fungi as multicellular structures consisting of somatic and reproductive cells—a feature independently evolved in animals and plants—has several functions, including the development of fruit bodies for dissemination of sexual spores (see above) and biofilms for substrate colonization and intercellular communication.

 

Fungi are traditionally considered heterotrophs, organisms that rely solely on carbon fixed by other organisms for metabolism. Fungi have evolved a high degree of metabolic versatility that allows them to use a diverse range of organic substrates for growth, including simple compounds such as nitrate, ammonia, acetate, or ethanol. In some species the pigment melanin may play a role in extracting energy from ionizing radiation, such as gamma radiation. This form of "radiotrophic" growth has been described for only a few species, the effects on growth rates are small, and the underlying biophysical and biochemical processes are not well known. This process might bear similarity to CO2 fixation via visible light, but instead uses ionizing radiation as a source of energy.

 

Reproduction

Two thickly stemmed brownish mushrooms with scales on the upper surface, growing out of a tree trunk

Polyporus squamosus

Fungal reproduction is complex, reflecting the differences in lifestyles and genetic makeup within this diverse kingdom of organisms. It is estimated that a third of all fungi reproduce using more than one method of propagation; for example, reproduction may occur in two well-differentiated stages within the life cycle of a species, the teleomorph (sexual reproduction) and the anamorph (asexual reproduction). Environmental conditions trigger genetically determined developmental states that lead to the creation of specialized structures for sexual or asexual reproduction. These structures aid reproduction by efficiently dispersing spores or spore-containing propagules.

 

Asexual reproduction

Asexual reproduction occurs via vegetative spores (conidia) or through mycelial fragmentation. Mycelial fragmentation occurs when a fungal mycelium separates into pieces, and each component grows into a separate mycelium. Mycelial fragmentation and vegetative spores maintain clonal populations adapted to a specific niche, and allow more rapid dispersal than sexual reproduction. The "Fungi imperfecti" (fungi lacking the perfect or sexual stage) or Deuteromycota comprise all the species that lack an observable sexual cycle. Deuteromycota (alternatively known as Deuteromycetes, conidial fungi, or mitosporic fungi) is not an accepted taxonomic clade and is now taken to mean simply fungi that lack a known sexual stage.

 

Sexual reproduction

See also: Mating in fungi and Sexual selection in fungi

Sexual reproduction with meiosis has been directly observed in all fungal phyla except Glomeromycota (genetic analysis suggests meiosis in Glomeromycota as well). It differs in many aspects from sexual reproduction in animals or plants. Differences also exist between fungal groups and can be used to discriminate species by morphological differences in sexual structures and reproductive strategies. Mating experiments between fungal isolates may identify species on the basis of biological species concepts. The major fungal groupings have initially been delineated based on the morphology of their sexual structures and spores; for example, the spore-containing structures, asci and basidia, can be used in the identification of ascomycetes and basidiomycetes, respectively. Fungi employ two mating systems: heterothallic species allow mating only between individuals of the opposite mating type, whereas homothallic species can mate, and sexually reproduce, with any other individual or itself.

 

Most fungi have both a haploid and a diploid stage in their life cycles. In sexually reproducing fungi, compatible individuals may combine by fusing their hyphae together into an interconnected network; this process, anastomosis, is required for the initiation of the sexual cycle. Many ascomycetes and basidiomycetes go through a dikaryotic stage, in which the nuclei inherited from the two parents do not combine immediately after cell fusion, but remain separate in the hyphal cells (see heterokaryosis).

 

In ascomycetes, dikaryotic hyphae of the hymenium (the spore-bearing tissue layer) form a characteristic hook (crozier) at the hyphal septum. During cell division, the formation of the hook ensures proper distribution of the newly divided nuclei into the apical and basal hyphal compartments. An ascus (plural asci) is then formed, in which karyogamy (nuclear fusion) occurs. Asci are embedded in an ascocarp, or fruiting body. Karyogamy in the asci is followed immediately by meiosis and the production of ascospores. After dispersal, the ascospores may germinate and form a new haploid mycelium.

 

Sexual reproduction in basidiomycetes is similar to that of the ascomycetes. Compatible haploid hyphae fuse to produce a dikaryotic mycelium. However, the dikaryotic phase is more extensive in the basidiomycetes, often also present in the vegetatively growing mycelium. A specialized anatomical structure, called a clamp connection, is formed at each hyphal septum. As with the structurally similar hook in the ascomycetes, the clamp connection in the basidiomycetes is required for controlled transfer of nuclei during cell division, to maintain the dikaryotic stage with two genetically different nuclei in each hyphal compartment. A basidiocarp is formed in which club-like structures known as basidia generate haploid basidiospores after karyogamy and meiosis. The most commonly known basidiocarps are mushrooms, but they may also take other forms (see Morphology section).

 

In fungi formerly classified as Zygomycota, haploid hyphae of two individuals fuse, forming a gametangium, a specialized cell structure that becomes a fertile gamete-producing cell. The gametangium develops into a zygospore, a thick-walled spore formed by the union of gametes. When the zygospore germinates, it undergoes meiosis, generating new haploid hyphae, which may then form asexual sporangiospores. These sporangiospores allow the fungus to rapidly disperse and germinate into new genetically identical haploid fungal mycelia.

 

Spore dispersal

The spores of most of the researched species of fungi are transported by wind. Such species often produce dry or hydrophobic spores that do not absorb water and are readily scattered by raindrops, for example. In other species, both asexual and sexual spores or sporangiospores are often actively dispersed by forcible ejection from their reproductive structures. This ejection ensures exit of the spores from the reproductive structures as well as traveling through the air over long distances.

 

Specialized mechanical and physiological mechanisms, as well as spore surface structures (such as hydrophobins), enable efficient spore ejection. For example, the structure of the spore-bearing cells in some ascomycete species is such that the buildup of substances affecting cell volume and fluid balance enables the explosive discharge of spores into the air. The forcible discharge of single spores termed ballistospores involves formation of a small drop of water (Buller's drop), which upon contact with the spore leads to its projectile release with an initial acceleration of more than 10,000 g; the net result is that the spore is ejected 0.01–0.02 cm, sufficient distance for it to fall through the gills or pores into the air below. Other fungi, like the puffballs, rely on alternative mechanisms for spore release, such as external mechanical forces. The hydnoid fungi (tooth fungi) produce spores on pendant, tooth-like or spine-like projections. The bird's nest fungi use the force of falling water drops to liberate the spores from cup-shaped fruiting bodies. Another strategy is seen in the stinkhorns, a group of fungi with lively colors and putrid odor that attract insects to disperse their spores.

 

Homothallism

In homothallic sexual reproduction, two haploid nuclei derived from the same individual fuse to form a zygote that can then undergo meiosis. Homothallic fungi include species with an Aspergillus-like asexual stage (anamorphs) occurring in numerous different genera, several species of the ascomycete genus Cochliobolus, and the ascomycete Pneumocystis jirovecii. The earliest mode of sexual reproduction among eukaryotes was likely homothallism, that is, self-fertile unisexual reproduction.

 

Other sexual processes

Besides regular sexual reproduction with meiosis, certain fungi, such as those in the genera Penicillium and Aspergillus, may exchange genetic material via parasexual processes, initiated by anastomosis between hyphae and plasmogamy of fungal cells. The frequency and relative importance of parasexual events is unclear and may be lower than other sexual processes. It is known to play a role in intraspecific hybridization and is likely required for hybridization between species, which has been associated with major events in fungal evolution.

 

Evolution

In contrast to plants and animals, the early fossil record of the fungi is meager. Factors that likely contribute to the under-representation of fungal species among fossils include the nature of fungal fruiting bodies, which are soft, fleshy, and easily degradable tissues and the microscopic dimensions of most fungal structures, which therefore are not readily evident. Fungal fossils are difficult to distinguish from those of other microbes, and are most easily identified when they resemble extant fungi. Often recovered from a permineralized plant or animal host, these samples are typically studied by making thin-section preparations that can be examined with light microscopy or transmission electron microscopy. Researchers study compression fossils by dissolving the surrounding matrix with acid and then using light or scanning electron microscopy to examine surface details.

 

The earliest fossils possessing features typical of fungi date to the Paleoproterozoic era, some 2,400 million years ago (Ma); these multicellular benthic organisms had filamentous structures capable of anastomosis. Other studies (2009) estimate the arrival of fungal organisms at about 760–1060 Ma on the basis of comparisons of the rate of evolution in closely related groups. The oldest fossilizied mycelium to be identified from its molecular composition is between 715 and 810 million years old. For much of the Paleozoic Era (542–251 Ma), the fungi appear to have been aquatic and consisted of organisms similar to the extant chytrids in having flagellum-bearing spores. The evolutionary adaptation from an aquatic to a terrestrial lifestyle necessitated a diversification of ecological strategies for obtaining nutrients, including parasitism, saprobism, and the development of mutualistic relationships such as mycorrhiza and lichenization. Studies suggest that the ancestral ecological state of the Ascomycota was saprobism, and that independent lichenization events have occurred multiple times.

 

In May 2019, scientists reported the discovery of a fossilized fungus, named Ourasphaira giraldae, in the Canadian Arctic, that may have grown on land a billion years ago, well before plants were living on land. Pyritized fungus-like microfossils preserved in the basal Ediacaran Doushantuo Formation (~635 Ma) have been reported in South China. Earlier, it had been presumed that the fungi colonized the land during the Cambrian (542–488.3 Ma), also long before land plants. Fossilized hyphae and spores recovered from the Ordovician of Wisconsin (460 Ma) resemble modern-day Glomerales, and existed at a time when the land flora likely consisted of only non-vascular bryophyte-like plants. Prototaxites, which was probably a fungus or lichen, would have been the tallest organism of the late Silurian and early Devonian. Fungal fossils do not become common and uncontroversial until the early Devonian (416–359.2 Ma), when they occur abundantly in the Rhynie chert, mostly as Zygomycota and Chytridiomycota. At about this same time, approximately 400 Ma, the Ascomycota and Basidiomycota diverged, and all modern classes of fungi were present by the Late Carboniferous (Pennsylvanian, 318.1–299 Ma).

 

Lichens formed a component of the early terrestrial ecosystems, and the estimated age of the oldest terrestrial lichen fossil is 415 Ma; this date roughly corresponds to the age of the oldest known sporocarp fossil, a Paleopyrenomycites species found in the Rhynie Chert. The oldest fossil with microscopic features resembling modern-day basidiomycetes is Palaeoancistrus, found permineralized with a fern from the Pennsylvanian. Rare in the fossil record are the Homobasidiomycetes (a taxon roughly equivalent to the mushroom-producing species of the Agaricomycetes). Two amber-preserved specimens provide evidence that the earliest known mushroom-forming fungi (the extinct species Archaeomarasmius leggetti) appeared during the late Cretaceous, 90 Ma.

 

Some time after the Permian–Triassic extinction event (251.4 Ma), a fungal spike (originally thought to be an extraordinary abundance of fungal spores in sediments) formed, suggesting that fungi were the dominant life form at this time, representing nearly 100% of the available fossil record for this period. However, the relative proportion of fungal spores relative to spores formed by algal species is difficult to assess, the spike did not appear worldwide, and in many places it did not fall on the Permian–Triassic boundary.

 

Sixty-five million years ago, immediately after the Cretaceous–Paleogene extinction event that famously killed off most dinosaurs, there was a dramatic increase in evidence of fungi; apparently the death of most plant and animal species led to a huge fungal bloom like "a massive compost heap".

 

Taxonomy

Although commonly included in botany curricula and textbooks, fungi are more closely related to animals than to plants and are placed with the animals in the monophyletic group of opisthokonts. Analyses using molecular phylogenetics support a monophyletic origin of fungi. The taxonomy of fungi is in a state of constant flux, especially due to research based on DNA comparisons. These current phylogenetic analyses often overturn classifications based on older and sometimes less discriminative methods based on morphological features and biological species concepts obtained from experimental matings.

 

There is no unique generally accepted system at the higher taxonomic levels and there are frequent name changes at every level, from species upwards. Efforts among researchers are now underway to establish and encourage usage of a unified and more consistent nomenclature. Until relatively recent (2012) changes to the International Code of Nomenclature for algae, fungi and plants, fungal species could also have multiple scientific names depending on their life cycle and mode (sexual or asexual) of reproduction. Web sites such as Index Fungorum and MycoBank are officially recognized nomenclatural repositories and list current names of fungal species (with cross-references to older synonyms).

 

The 2007 classification of Kingdom Fungi is the result of a large-scale collaborative research effort involving dozens of mycologists and other scientists working on fungal taxonomy. It recognizes seven phyla, two of which—the Ascomycota and the Basidiomycota—are contained within a branch representing subkingdom Dikarya, the most species rich and familiar group, including all the mushrooms, most food-spoilage molds, most plant pathogenic fungi, and the beer, wine, and bread yeasts. The accompanying cladogram depicts the major fungal taxa and their relationship to opisthokont and unikont organisms, based on the work of Philippe Silar, "The Mycota: A Comprehensive Treatise on Fungi as Experimental Systems for Basic and Applied Research" and Tedersoo et al. 2018. The lengths of the branches are not proportional to evolutionary distances.

 

The major phyla (sometimes called divisions) of fungi have been classified mainly on the basis of characteristics of their sexual reproductive structures. As of 2019, nine major lineages have been identified: Opisthosporidia, Chytridiomycota, Neocallimastigomycota, Blastocladiomycota, Zoopagomycotina, Mucoromycota, Glomeromycota, Ascomycota and Basidiomycota.

 

Phylogenetic analysis has demonstrated that the Microsporidia, unicellular parasites of animals and protists, are fairly recent and highly derived endobiotic fungi (living within the tissue of another species). Previously considered to be "primitive" protozoa, they are now thought to be either a basal branch of the Fungi, or a sister group–each other's closest evolutionary relative.

 

The Chytridiomycota are commonly known as chytrids. These fungi are distributed worldwide. Chytrids and their close relatives Neocallimastigomycota and Blastocladiomycota (below) are the only fungi with active motility, producing zoospores that are capable of active movement through aqueous phases with a single flagellum, leading early taxonomists to classify them as protists. Molecular phylogenies, inferred from rRNA sequences in ribosomes, suggest that the Chytrids are a basal group divergent from the other fungal phyla, consisting of four major clades with suggestive evidence for paraphyly or possibly polyphyly.

 

The Blastocladiomycota were previously considered a taxonomic clade within the Chytridiomycota. Molecular data and ultrastructural characteristics, however, place the Blastocladiomycota as a sister clade to the Zygomycota, Glomeromycota, and Dikarya (Ascomycota and Basidiomycota). The blastocladiomycetes are saprotrophs, feeding on decomposing organic matter, and they are parasites of all eukaryotic groups. Unlike their close relatives, the chytrids, most of which exhibit zygotic meiosis, the blastocladiomycetes undergo sporic meiosis.

 

The Neocallimastigomycota were earlier placed in the phylum Chytridiomycota. Members of this small phylum are anaerobic organisms, living in the digestive system of larger herbivorous mammals and in other terrestrial and aquatic environments enriched in cellulose (e.g., domestic waste landfill sites). They lack mitochondria but contain hydrogenosomes of mitochondrial origin. As in the related chrytrids, neocallimastigomycetes form zoospores that are posteriorly uniflagellate or polyflagellate.

 

Microscopic view of a layer of translucent grayish cells, some containing small dark-color spheres

Arbuscular mycorrhiza seen under microscope. Flax root cortical cells containing paired arbuscules.

Cross-section of a cup-shaped structure showing locations of developing meiotic asci (upper edge of cup, left side, arrows pointing to two gray cells containing four and two small circles), sterile hyphae (upper edge of cup, right side, arrows pointing to white cells with a single small circle in them), and mature asci (upper edge of cup, pointing to two gray cells with eight small circles in them)

Diagram of an apothecium (the typical cup-like reproductive structure of Ascomycetes) showing sterile tissues as well as developing and mature asci.

Members of the Glomeromycota form arbuscular mycorrhizae, a form of mutualist symbiosis wherein fungal hyphae invade plant root cells and both species benefit from the resulting increased supply of nutrients. All known Glomeromycota species reproduce asexually. The symbiotic association between the Glomeromycota and plants is ancient, with evidence dating to 400 million years ago. Formerly part of the Zygomycota (commonly known as 'sugar' and 'pin' molds), the Glomeromycota were elevated to phylum status in 2001 and now replace the older phylum Zygomycota. Fungi that were placed in the Zygomycota are now being reassigned to the Glomeromycota, or the subphyla incertae sedis Mucoromycotina, Kickxellomycotina, the Zoopagomycotina and the Entomophthoromycotina. Some well-known examples of fungi formerly in the Zygomycota include black bread mold (Rhizopus stolonifer), and Pilobolus species, capable of ejecting spores several meters through the air. Medically relevant genera include Mucor, Rhizomucor, and Rhizopus.

 

The Ascomycota, commonly known as sac fungi or ascomycetes, constitute the largest taxonomic group within the Eumycota. These fungi form meiotic spores called ascospores, which are enclosed in a special sac-like structure called an ascus. This phylum includes morels, a few mushrooms and truffles, unicellular yeasts (e.g., of the genera Saccharomyces, Kluyveromyces, Pichia, and Candida), and many filamentous fungi living as saprotrophs, parasites, and mutualistic symbionts (e.g. lichens). Prominent and important genera of filamentous ascomycetes include Aspergillus, Penicillium, Fusarium, and Claviceps. Many ascomycete species have only been observed undergoing asexual reproduction (called anamorphic species), but analysis of molecular data has often been able to identify their closest teleomorphs in the Ascomycota. Because the products of meiosis are retained within the sac-like ascus, ascomycetes have been used for elucidating principles of genetics and heredity (e.g., Neurospora crassa).

 

Members of the Basidiomycota, commonly known as the club fungi or basidiomycetes, produce meiospores called basidiospores on club-like stalks called basidia. Most common mushrooms belong to this group, as well as rust and smut fungi, which are major pathogens of grains. Other important basidiomycetes include the maize pathogen Ustilago maydis, human commensal species of the genus Malassezia, and the opportunistic human pathogen, Cryptococcus neoformans.

 

Fungus-like organisms

Because of similarities in morphology and lifestyle, the slime molds (mycetozoans, plasmodiophorids, acrasids, Fonticula and labyrinthulids, now in Amoebozoa, Rhizaria, Excavata, Opisthokonta and Stramenopiles, respectively), water molds (oomycetes) and hyphochytrids (both Stramenopiles) were formerly classified in the kingdom Fungi, in groups like Mastigomycotina, Gymnomycota and Phycomycetes. The slime molds were studied also as protozoans, leading to an ambiregnal, duplicated taxonomy.

 

Unlike true fungi, the cell walls of oomycetes contain cellulose and lack chitin. Hyphochytrids have both chitin and cellulose. Slime molds lack a cell wall during the assimilative phase (except labyrinthulids, which have a wall of scales), and take in nutrients by ingestion (phagocytosis, except labyrinthulids) rather than absorption (osmotrophy, as fungi, labyrinthulids, oomycetes and hyphochytrids). Neither water molds nor slime molds are closely related to the true fungi, and, therefore, taxonomists no longer group them in the kingdom Fungi. Nonetheless, studies of the oomycetes and myxomycetes are still often included in mycology textbooks and primary research literature.

 

The Eccrinales and Amoebidiales are opisthokont protists, previously thought to be zygomycete fungi. Other groups now in Opisthokonta (e.g., Corallochytrium, Ichthyosporea) were also at given time classified as fungi. The genus Blastocystis, now in Stramenopiles, was originally classified as a yeast. Ellobiopsis, now in Alveolata, was considered a chytrid. The bacteria were also included in fungi in some classifications, as the group Schizomycetes.

 

The Rozellida clade, including the "ex-chytrid" Rozella, is a genetically disparate group known mostly from environmental DNA sequences that is a sister group to fungi. Members of the group that have been isolated lack the chitinous cell wall that is characteristic of fungi. Alternatively, Rozella can be classified as a basal fungal group.

 

The nucleariids may be the next sister group to the eumycete clade, and as such could be included in an expanded fungal kingdom. Many Actinomycetales (Actinomycetota), a group with many filamentous bacteria, were also long believed to be fungi.

 

Ecology

Although often inconspicuous, fungi occur in every environment on Earth and play very important roles in most ecosystems. Along with bacteria, fungi are the major decomposers in most terrestrial (and some aquatic) ecosystems, and therefore play a critical role in biogeochemical cycles and in many food webs. As decomposers, they play an essential role in nutrient cycling, especially as saprotrophs and symbionts, degrading organic matter to inorganic molecules, which can then re-enter anabolic metabolic pathways in plants or other organisms.

 

Symbiosis

Many fungi have important symbiotic relationships with organisms from most if not all kingdoms. These interactions can be mutualistic or antagonistic in nature, or in the case of commensal fungi are of no apparent benefit or detriment to the host.

 

With plants

Mycorrhizal symbiosis between plants and fungi is one of the most well-known plant–fungus associations and is of significant importance for plant growth and persistence in many ecosystems; over 90% of all plant species engage in mycorrhizal relationships with fungi and are dependent upon this relationship for survival.

 

A microscopic view of blue-stained cells, some with dark wavy lines in them

The dark filaments are hyphae of the endophytic fungus Epichloë coenophiala in the intercellular spaces of tall fescue leaf sheath tissue

The mycorrhizal symbiosis is ancient, dating back to at least 400 million years. It often increases the plant's uptake of inorganic compounds, such as nitrate and phosphate from soils having low concentrations of these key plant nutrients. The fungal partners may also mediate plant-to-plant transfer of carbohydrates and other nutrients. Such mycorrhizal communities are called "common mycorrhizal networks". A special case of mycorrhiza is myco-heterotrophy, whereby the plant parasitizes the fungus, obtaining all of its nutrients from its fungal symbiont. Some fungal species inhabit the tissues inside roots, stems, and leaves, in which case they are called endophytes. Similar to mycorrhiza, endophytic colonization by fungi may benefit both symbionts; for example, endophytes of grasses impart to their host increased resistance to herbivores and other environmental stresses and receive food and shelter from the plant in return.

 

With algae and cyanobacteria

A green, leaf-like structure attached to a tree, with a pattern of ridges and depression on the bottom surface

The lichen Lobaria pulmonaria, a symbiosis of fungal, algal, and cyanobacterial species

Lichens are a symbiotic relationship between fungi and photosynthetic algae or cyanobacteria. The photosynthetic partner in the relationship is referred to in lichen terminology as a "photobiont". The fungal part of the relationship is composed mostly of various species of ascomycetes and a few basidiomycetes. Lichens occur in every ecosystem on all continents, play a key role in soil formation and the initiation of biological succession, and are prominent in some extreme environments, including polar, alpine, and semiarid desert regions. They are able to grow on inhospitable surfaces, including bare soil, rocks, tree bark, wood, shells, barnacles and leaves. As in mycorrhizas, the photobiont provides sugars and other carbohydrates via photosynthesis to the fungus, while the fungus provides minerals and water to the photobiont. The functions of both symbiotic organisms are so closely intertwined that they function almost as a single organism; in most cases the resulting organism differs greatly from the individual components. Lichenization is a common mode of nutrition for fungi; around 27% of known fungi—more than 19,400 species—are lichenized. Characteristics common to most lichens include obtaining organic carbon by photosynthesis, slow growth, small size, long life, long-lasting (seasonal) vegetative reproductive structures, mineral nutrition obtained largely from airborne sources, and greater tolerance of desiccation than most other photosynthetic organisms in the same habitat.

 

With insects

Many insects also engage in mutualistic relationships with fungi. Several groups of ants cultivate fungi in the order Chaetothyriales for several purposes: as a food source, as a structural component of their nests, and as a part of an ant/plant symbiosis in the domatia (tiny chambers in plants that house arthropods). Ambrosia beetles cultivate various species of fungi in the bark of trees that they infest. Likewise, females of several wood wasp species (genus Sirex) inject their eggs together with spores of the wood-rotting fungus Amylostereum areolatum into the sapwood of pine trees; the growth of the fungus provides ideal nutritional conditions for the development of the wasp larvae. At least one species of stingless bee has a relationship with a fungus in the genus Monascus, where the larvae consume and depend on fungus transferred from old to new nests. Termites on the African savannah are also known to cultivate fungi, and yeasts of the genera Candida and Lachancea inhabit the gut of a wide range of insects, including neuropterans, beetles, and cockroaches; it is not known whether these fungi benefit their hosts. Fungi growing in dead wood are essential for xylophagous insects (e.g. woodboring beetles). They deliver nutrients needed by xylophages to nutritionally scarce dead wood. Thanks to this nutritional enrichment the larvae of the woodboring insect is able to grow and develop to adulthood. The larvae of many families of fungicolous flies, particularly those within the superfamily Sciaroidea such as the Mycetophilidae and some Keroplatidae feed on fungal fruiting bodies and sterile mycorrhizae.

 

A thin brown stick positioned horizontally with roughly two dozen clustered orange-red leaves originating from a single point in the middle of the stick. These orange leaves are three to four times larger than the few other green leaves growing out of the stick, and are covered on the lower leaf surface with hundreds of tiny bumps. The background shows the green leaves and branches of neighboring shrubs.

The plant pathogen Puccinia magellanicum (calafate rust) causes the defect known as witch's broom, seen here on a barberry shrub in Chile.

 

Gram stain of Candida albicans from a vaginal swab from a woman with candidiasis, showing hyphae, and chlamydospores, which are 2–4 µm in diameter.

Many fungi are parasites on plants, animals (including humans), and other fungi. Serious pathogens of many cultivated plants causing extensive damage and losses to agriculture and forestry include the rice blast fungus Magnaporthe oryzae, tree pathogens such as Ophiostoma ulmi and Ophiostoma novo-ulmi causing Dutch elm disease, Cryphonectria parasitica responsible for chestnut blight, and Phymatotrichopsis omnivora causing Texas Root Rot, and plant pathogens in the genera Fusarium, Ustilago, Alternaria, and Cochliobolus. Some carnivorous fungi, like Paecilomyces lilacinus, are predators of nematodes, which they capture using an array of specialized structures such as constricting rings or adhesive nets. Many fungi that are plant pathogens, such as Magnaporthe oryzae, can switch from being biotrophic (parasitic on living plants) to being necrotrophic (feeding on the dead tissues of plants they have killed). This same principle is applied to fungi-feeding parasites, including Asterotremella albida, which feeds on the fruit bodies of other fungi both while they are living and after they are dead.

 

Some fungi can cause serious diseases in humans, several of which may be fatal if untreated. These include aspergillosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mycetomas, and paracoccidioidomycosis. Furthermore, persons with immuno-deficiencies are particularly susceptible to disease by genera such as Aspergillus, Candida, Cryptoccocus, Histoplasma, and Pneumocystis. Other fungi can attack eyes, nails, hair, and especially skin, the so-called dermatophytic and keratinophilic fungi, and cause local infections such as ringworm and athlete's foot. Fungal spores are also a cause of allergies, and fungi from different taxonomic groups can evoke allergic reactions.

 

As targets of mycoparasites

Organisms that parasitize fungi are known as mycoparasitic organisms. About 300 species of fungi and fungus-like organisms, belonging to 13 classes and 113 genera, are used as biocontrol agents against plant fungal diseases. Fungi can also act as mycoparasites or antagonists of other fungi, such as Hypomyces chrysospermus, which grows on bolete mushrooms. Fungi can also become the target of infection by mycoviruses.

 

Communication

Main article: Mycorrhizal networks

There appears to be electrical communication between fungi in word-like components according to spiking characteristics.

 

Possible impact on climate

According to a study published in the academic journal Current Biology, fungi can soak from the atmosphere around 36% of global fossil fuel greenhouse gas emissions.

 

Mycotoxins

(6aR,9R)-N-((2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-2H-oxazolo[3,2-a] pyrrolo[2,1-c]pyrazin-2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg] quinoline-9-carboxamide

Ergotamine, a major mycotoxin produced by Claviceps species, which if ingested can cause gangrene, convulsions, and hallucinations

Many fungi produce biologically active compounds, several of which are toxic to animals or plants and are therefore called mycotoxins. Of particular relevance to humans are mycotoxins produced by molds causing food spoilage, and poisonous mushrooms (see above). Particularly infamous are the lethal amatoxins in some Amanita mushrooms, and ergot alkaloids, which have a long history of causing serious epidemics of ergotism (St Anthony's Fire) in people consuming rye or related cereals contaminated with sclerotia of the ergot fungus, Claviceps purpurea. Other notable mycotoxins include the aflatoxins, which are insidious liver toxins and highly carcinogenic metabolites produced by certain Aspergillus species often growing in or on grains and nuts consumed by humans, ochratoxins, patulin, and trichothecenes (e.g., T-2 mycotoxin) and fumonisins, which have significant impact on human food supplies or animal livestock.

 

Mycotoxins are secondary metabolites (or natural products), and research has established the existence of biochemical pathways solely for the purpose of producing mycotoxins and other natural products in fungi. Mycotoxins may provide fitness benefits in terms of physiological adaptation, competition with other microbes and fungi, and protection from consumption (fungivory). Many fungal secondary metabolites (or derivatives) are used medically, as described under Human use below.

 

Pathogenic mechanisms

Ustilago maydis is a pathogenic plant fungus that causes smut disease in maize and teosinte. Plants have evolved efficient defense systems against pathogenic microbes such as U. maydis. A rapid defense reaction after pathogen attack is the oxidative burst where the plant produces reactive oxygen species at the site of the attempted invasion. U. maydis can respond to the oxidative burst with an oxidative stress response, regulated by the gene YAP1. The response protects U. maydis from the host defense, and is necessary for the pathogen's virulence. Furthermore, U. maydis has a well-established recombinational DNA repair system which acts during mitosis and meiosis. The system may assist the pathogen in surviving DNA damage arising from the host plant's oxidative defensive response to infection.

 

Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. C. neoformans usually infects the lungs, where it is phagocytosed by alveolar macrophages. Some C. neoformans can survive inside macrophages, which appears to be the basis for latency, disseminated disease, and resistance to antifungal agents. One mechanism by which C. neoformans survives the hostile macrophage environment is by up-regulating the expression of genes involved in the oxidative stress response. Another mechanism involves meiosis. The majority of C. neoformans are mating "type a". Filaments of mating "type a" ordinarily have haploid nuclei, but they can become diploid (perhaps by endoduplication or by stimulated nuclear fusion) to form blastospores. The diploid nuclei of blastospores can undergo meiosis, including recombination, to form haploid basidiospores that can be dispersed. This process is referred to as monokaryotic fruiting. This process requires a gene called DMC1, which is a conserved homologue of genes recA in bacteria and RAD51 in eukaryotes, that mediates homologous chromosome pairing during meiosis and repair of DNA double-strand breaks. Thus, C. neoformans can undergo a meiosis, monokaryotic fruiting, that promotes recombinational repair in the oxidative, DNA damaging environment of the host macrophage, and the repair capability may contribute to its virulence.

 

Human use

See also: Human interactions with fungi

Microscopic view of five spherical structures; one of the spheres is considerably smaller than the rest and attached to one of the larger spheres

Saccharomyces cerevisiae cells shown with DIC microscopy

The human use of fungi for food preparation or preservation and other purposes is extensive and has a long history. Mushroom farming and mushroom gathering are large industries in many countries. The study of the historical uses and sociological impact of fungi is known as ethnomycology. Because of the capacity of this group to produce an enormous range of natural products with antimicrobial or other biological activities, many species have long been used or are being developed for industrial production of antibiotics, vitamins, and anti-cancer and cholesterol-lowering drugs. Methods have been developed for genetic engineering of fungi, enabling metabolic engineering of fungal species. For example, genetic modification of yeast species—which are easy to grow at fast rates in large fermentation vessels—has opened up ways of pharmaceutical production that are potentially more efficient than production by the original source organisms. Fungi-based industries are sometimes considered to be a major part of a growing bioeconomy, with applications under research and development including use for textiles, meat substitution and general fungal biotechnology.

 

Therapeutic uses

Modern chemotherapeutics

Many species produce metabolites that are major sources of pharmacologically active drugs.

 

Antibiotics

Particularly important are the antibiotics, including the penicillins, a structurally related group of β-lactam antibiotics that are synthesized from small peptides. Although naturally occurring penicillins such as penicillin G (produced by Penicillium chrysogenum) have a relatively narrow spectrum of biological activity, a wide range of other penicillins can be produced by chemical modification of the natural penicillins. Modern penicillins are semisynthetic compounds, obtained initially from fermentation cultures, but then structurally altered for specific desirable properties. Other antibiotics produced by fungi include: ciclosporin, commonly used as an immunosuppressant during transplant surgery; and fusidic acid, used to help control infection from methicillin-resistant Staphylococcus aureus bacteria. Widespread use of antibiotics for the treatment of bacterial diseases, such as tuberculosis, syphilis, leprosy, and others began in the early 20th century and continues to date. In nature, antibiotics of fungal or bacterial origin appear to play a dual role: at high concentrations they act as chemical defense against competition with other microorganisms in species-rich environments, such as the rhizosphere, and at low concentrations as quorum-sensing molecules for intra- or interspecies signaling.

 

Other

Other drugs produced by fungi include griseofulvin isolated from Penicillium griseofulvum, used to treat fungal infections, and statins (HMG-CoA reductase inhibitors), used to inhibit cholesterol synthesis. Examples of statins found in fungi include mevastatin from Penicillium citrinum and lovastatin from Aspergillus terreus and the oyster mushroom. Psilocybin from fungi is investigated for therapeutic use and appears to cause global increases in brain network integration. Fungi produce compounds that inhibit viruses and cancer cells. Specific metabolites, such as polysaccharide-K, ergotamine, and β-lactam antibiotics, are routinely used in clinical medicine. The shiitake mushroom is a source of lentinan, a clinical drug approved for use in cancer treatments in several countries, including Japan. In Europe and Japan, polysaccharide-K (brand name Krestin), a chemical derived from Trametes versicolor, is an approved adjuvant for cancer therapy.

 

Traditional medicine

Upper surface view of a kidney-shaped fungus, brownish-red with a lighter yellow-brown margin, and a somewhat varnished or shiny appearance

Two dried yellow-orange caterpillars, one with a curly grayish fungus growing out of one of its ends. The grayish fungus is roughly equal to or slightly greater in length than the caterpillar, and tapers in thickness to a narrow end.

The fungi Ganoderma lucidum (left) and Ophiocordyceps sinensis (right) are used in traditional medicine practices

Certain mushrooms are used as supposed therapeutics in folk medicine practices, such as traditional Chinese medicine. Mushrooms with a history of such use include Agaricus subrufescens, Ganoderma lucidum, and Ophiocordyceps sinensis.

 

Cultured foods

Baker's yeast or Saccharomyces cerevisiae, a unicellular fungus, is used to make bread and other wheat-based products, such as pizza dough and dumplings. Yeast species of the genus Saccharomyces are also used to produce alcoholic beverages through fermentation. Shoyu koji mold (Aspergillus oryzae) is an essential ingredient in brewing Shoyu (soy sauce) and sake, and the preparation of miso while Rhizopus species are used for making tempeh. Several of these fungi are domesticated species that were bred or selected according to their capacity to ferment food without producing harmful mycotoxins (see below), which are produced by very closely related Aspergilli. Quorn, a meat substitute, is made from Fusarium venenatum.

Les blousons noirs sont une sous-culture juvénile apparue en France dans les années 1950 et qui a connu son apogée entre 1958 et 1961. Issue de l'influence américaine, connotée à un code vestimentaire particulier et au rock'n roll, elle a été la matrice originelle du mouvement yéyé et de quasiment toutes les modes adolescentes ultérieures. Des sous-cultures similaires ont fleuri au même moment dans d'autres pays d'Europe.

La culture « blouson noir » s'est cristallisée autour d'importations américaines qui ont été autant de chocs culturels :

Le film L'Équipée sauvage (The Wild One), sorti en 1953 aux États-Unis mais popularisé courant 1955 en Europe, où le personnage interprété par Marlon Brando révèle d'un coup une façon d'être qui fait époque : cuir noir, moto, machisme, volonté de choquer, esprit de gang, violence à la limite de la criminalité.

Un autre film, La Fureur de vivre (Rebel Without a Cause) arrive en 1956 en France et fait de James Dean une icône définitive. Il introduit l'idée importante que le comportement des (futurs) blousons noirs n'est pas seulement un choix délibéré mais procède d'une fatalité générationnelle et de l'incompréhension des adultes.

L'arrivée au même moment du rock'n roll (Bill Haley et Elvis Presley en premier lieu, puis Gene Vincent, Eddie Cochran etc.) ajoute le son à l'image. Mais c'est une chanteuse française a priori non associée au rock'n roll qui apporte en 1956 une énorme visibilité médiatique au phénomène en formation, Édith Piaf, avec la chanson L'Homme à la moto, indirectement inspirée par L'Équipée sauvage.C'est durant l'été 1959 que l'appellation « blousons noirs » apparaît pour la première fois dans la presse, avec un article de France-Soir du 27 juillet 1959 relatant un affrontement entre bandes survenu au Square Saint-Lambert, dans le XVe arrondissement de Paris[1]. Cette désignation s'impose soudain comme synonyme de « jeunes voyous ». Les journaux se mettent alors à surenchérir en évoquant des bandes caractérisées par leur taille importante (il est question de groupes comptant jusqu'à une centaine de jeunes) et par leur violence. Les « blousons noirs » sont décrits comme des asociaux qui se battent à coups de chaînes de vélo (ou de moto), de coups de poing américains voire de couteaux à cran d'arrêt, qui cherchent la bagarre pour défendre leurs territoires urbains, particulièrement autour des portes de Paris, ou en faisant des descentes dans des bals ou des fêtes.Peu après, les journalistes forgèrent le terme « blousons dorés » pour désigner les jeunes fils de la bourgeoisie qui se faisaient remarquer dans les faits divers, par opposition aux « blousons noirs » qui étaient plutôt issus de milieux populaires.

Cette campagne de presse, qui tourne à la psychose collective, aura pour principal effet de mettre en vogue le genre blouson noir. Autour de 1960, dans tout le pays et dans tous les milieux sociaux, les jeunes gens à la mode aiment à s'habiller de cuir (mais le véritable Perfecto est encore rarissime), portent de grosses chemises à carreaux, se coiffent en arrière avec au sommet du front une large boucle asymétrique souvent brillantinée (la célèbre « banane »). À défaut d'une véritable moto, luxe accessible seulement aux plus fortunés, on roule sur des cyclomoteurs qui en ont à peu près l'aspect, de préférence une Flandria ou une Paloma, une mobylette à la rigueur. La petite délinquance est répandue dans ce milieu, sans être généralisée. Mais afin de choquer, les blousons noirs (qui se nomment eux-mêmes « loulous ») affectent de jouer les durs et de parler des argots empruntés au monde des truands.Ce milieu fournit la base sociale qui sera le marché initial du rock français. Il trouve ses héros en Johnny Hallyday, Eddy Mitchell et spécialement Vince Taylor, avant que la vague yéyé ne relègue au second plan les blousons noirs, à partir de 1963, le tournant a lieu le 22 juin 1963, lors de la « folle nuit de la Nation » : un concert gratuit organisé par Salut les Copains à Paris sur la Place de la Nation attire une immense foule, des incidents graves ont lieu, attribués (à tort ou à raison) à des bandes de blousons noirs. La scène yéyé prend définitivement ses distances avec ces derniers.

Les sociologues qui se penchaient alors sur les origines du problème de la délinquance juvénile évoquaient un conflit de génération ou une révolte contre l'ordre établi, avant d'avancer des facteurs économiques.La thèse la plus courante suggère que les jeunes de tous les pays ayant connu les privations de l'après-guerre se sont lancés à corps perdu dans la recherche de la liberté et le plaisir, voulant jouir immédiatement des biens que la société de consommations leur proposait: musique, moto ou mode. Mais pas assez riche pour pouvoir se les procurer et s'apercevant que la société n'était pas disposée à modifier ses habitudes, ni à ne leur faire aucune concession, ils se révoltèrent et leur enthousiasme se transforma en violence.

D'autres enquêtes au début des années soixante contestent cette thèse en soulignant l'importance de l'urbanisation dans le malaise des jeunes en mettant l'accent sur la concentration de grands ensembles immobiliers dans les villes véritables fabrique de blousons noirs.

"Les cités industrielles sont surtout pathogènes parce qu'elles favorisent les rassemblements de jeunes gens sur un territoire restreint " (109)

Effectivement, les bandes urbaines profilent surtout dans les quartiers abritant des grands immeubles collectifs type HLM ou des groupes d'habitations à bon marché souvent insalubre. Si les blocs HLM marquent un progrès certain par rapport au taudis, l'essentiel y manque trop souvent. La plus part du temps, il n'y a ni jardins, ni espace, ni équipement sportif sans parler de l'absence totale de distraction. Les enfants et les adolescents ont le sentiment d'être en cage et la rue les attire comme un refuge mauvais.

"On ne sait pas quoi faire, racontent des adolescents. Alors on se retrouve et on s'ennuie ensemble "

Parmi les autres facteurs on évoque souvent la carence d'autorité, mais c'est surtout dans la carence du milieu familial qu'il faut rechercher l'origine du drame des blousons noirs ; famille désagrégée, séparations ou divorces, alcoolisme du père.

Pour Henri Joubrel ; la dissociation familiale est la cause essentielle de la conduite asociale d'un nombre grandissant de jeune. Les statistiques montrent que 80 % des jeunes inadaptés sociaux dont on connaît suffisamment l'histoire pour en établir un dossier approfondi sortent d'un foyer dissocié. (111)

Au foyer, ils se sentent mal aimés, les gosses souhaitent la chaleur, ils trouvent le chaos

" Un soir en rentrant chez ma mère elle m'a virée, elle avait un jules " raconte Momo de la bande des Batignolles, après avoir traîné quelques jours dans les rues, le tribunal lui trouvera une famille d'accueil. (112)

" A quatorze ans, je suis parti travailler. Plâtrier. Pourquoi ? Parce que mon père boit et ma mère aussi ". écrit Jean dans Rallye Jeunesse (113)

Ce qui fait dire à un éducateur lyonnais :

" Ce qui déboussole souvent les jeunes, c'est l'impossibilité de prendre leur père pour modèle"

(114)

Si la société cherche les causes du mal dont souffre la jeunesse un autre facteur souvent négligé réside certainement dans le fait qu'ils sont victime de l'incompréhension des adultes. L'emblématique film " La Fureur de Vivre " évoquait déjà ces relations difficiles entre parents et enfant. A la question "mentez--vous à vos parents" posé par un journaliste qui enquête pour un hebdomadaire sur les problèmes de la jeunesse, des jeunes répondent :

" On ne ment pas, on ne parle pas ".

Puis lorsqu'il leur demande : " Que leur reprochez-vous ? ",

ils répondent: " Ils font vraiment une trop sale gueule à table ! " 58 (47)

Dans la même logique , une jeune fille, Raymonde écrit à Rallye Jeunesse

" Ce dont on souffre, c'est de l'ambiance familiale, du manque de vérité, de l'injustice de ce que nous appelons la "vague des croulants" " (116)Dans le conflit adultes jeunes, on assiste même à des faits incroyables comme histoire révélé par l'Humanité ou des jeunes émules des blousons noirs qui pétaradaient la nuit en scooter troublant le sommeil des citoyens de deux patelins ont été tondues par quelques habitants.

" La tête base, le crâne soigneusement tondu, suivant leur chef de fil qui de surcroît avait été dépouillé de son pantalon, plusieurs jeunes gens ont et promené dans les rues de Charly et de Vernaison près de Lyon sous l'œil marqué de la population… " (117)

109 « Les blousons noirs : une société primitive ? » - H.Michel (Directeur du centre de Vaucresson) – J.Selosse (Chargé de recherche au CNRS), In Sciences Avenir N°211, septembre 1964.

110 – « Les blousons noirs : une société primitive ? »

111 – « Mauvais garçons de bonnes familles » Henri Joubrel, Aubier, Editions Montaigne,1959

112 – « Square des Batignoles », Cinq colonnes à la une, 04/11/1960

113 - « Vous avez la parole », in Rallye Jeunesse N°11, février 1960.

114 – « Les garçons sauvage, le blouson noir, une provocateur mais aussi un mal aimé » Le Progrès de Lyon,09/12/1962

115 - "Mauvais garçons de bonnes familles" Henri Joubrel

116 – « Vous avez la parole », in Rallye Jeunesse N°11, février 1960

117 – « Tondeuse pour porteur de blousons », L’humanité, 21 juillet 1961 Si la bande est sociale dans sa structure, elle est par contre anti -sociale par son activité et par sa fonction. Si à l'origine elle ne semble pas se constituer dans un but délinquant, la bande est perçue sous cette forme par la police et la société. En réalité beaucoup de jeunes blousons noirs adoptaient uniquement un mode de comportement sans verser dans la délinquance mais s'exposaient de part ce fait à la réprobation sociale et à la répression. La plupart du temps les actes délictueux ne sont pas prémédités et sont commis dans l'inconscience la plus complète. On cherche surtout à réaliser un coup pour se valoriser sans vraiment se rendre compte de la gravité du délit.

" Ils ne se préoccupent pas exagérément des ennuis qu'ils ont eux avec la justice et ne s'inquiètent pas à l'idée d'avoir un casier judiciaire "(93)

Les Coeurs verts Edouard Luntz (cahiers du cinéma)

Les deux tiers des délits reprochés aux adolescents délinquants sont commis contre la propriété, dont les formes essentielles sont : le vol, les délits visant les deux roues et les actes de vandalisme.

Exemple type de l'activité d'une bande ; celle d'Arpajon dont la police a arrêté le mois de décembre 1959 une vingtaine de membres. Ces garçons âgés de 14 à 18 ans qui suivaient la plupart des cours professionnels dans la région parisienne, se réunissaient chaque jour sur le pont de l'Orge pour y préparer leurs "coups".

" Ils essayaient des blousons en plastique noir et se sauvaient sans les payer. Ils chipaient des disques, pour les écouter ou les revendre. Ils volaient des scooters et des voitures qu'ils abandonnaient hors d'usage. Ils faisaient main basse sur le contenu des autos en stationnement. Ils crevaient les pneus, allumaient des incendies ". (94)

Des adolescents par manque d'argent de poche pratiquent le vol à la tire et certain n'hésitent pas à faire les sacs des veilles dame. Le vol à l'étalage sert des fois pour l'alimentation des surboums. Le vol a parfois l'aspect d'un jeu, d'un défi lancé aux règles sociales.

Les objets volés sont souvent considérés comme des trophées et planqués dans des repaires. C'était le cas pour une bande de Nancy dont les exploits consistaient à voler les objets les plus hétéroclites au cours de cambriolage pour les tenir stockés dans une cave. Le chef de la bande âgé de 16 ans n'a pas hésité à tirer avec une carabine sur les inspecteurs de police venue les arrêter. Ce qui vaudra les assises à trois mineurs. Dans la même région à Charleville, un groupe de six mineurs de 14 et 15 ans connus sous le nom de " La bande des blousons verts " dirigé par un garçon de 20 ans commet 24 vols et cambriolages, le plus souvent la nuit, par effraction. (95)

Dans la région bordelaise chaque membre du gang des As avait son casier dans le garage abandonné qui leur servait de Q.G. on y trouvait les objets les plus hétéroclites, sous-vêtements féminins, couteaux, fer à repasser, boîtes de conserve, appareils photos, jouets, chapelets, rasoirs, statue religieuse etc. Leurs plus beaux trophées; une plaque minéralogique de car de Police Secours qu'ils conservaient jalousement dans leur repaire (96)

Certaines bandes étaient spécialisées dans le casse, lors d'un interrogatoire un jeune raconte avec cynisme ses exploits :

" En pleine nuit, quand nos parents dormaient, on se sauvait et on se retrouvait là... Là, on buvait pour se donner du courage, on s'habillait, on emportait la matraque, et on y allait. On s'habillait tous pareil, avec un masque, pour ne pas être reconnus. Ca commençait par les vitrines des petites veilles. On fait le coup en quelques secondes, à grands coups de matraques. On se donne même pas la peine de voler, ça ne nous intéresse pas... juste une bricole en guise de souvenir. Après le casse on se sauvait en vitesse par des ruelles d'où on n'avait rien pu entendre. On revenait fêter ça et on allait se coucher " (97)

  

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99) Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99)

Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

 

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

« LA SOCIETE NOUS AIME PAS, NOUS LES JEUNES ! »

Serge de la bande du Square des Batignolles (Cinq colonnes à la une 1960)

« Ces adolescents effondrés contre les murs, à la manière des cow-boys des westerns le long des cloisons des saloons, sont capables brusquement de lever le cran d'arrêt de leur énergie. Une poussée irrésistible les portes à imiter le Marlo Brando de l'Equipée Sauvage ou le James Dean de la Fureur de vivre"

Henri Joubrel, Jeunesse en danger, Fayard,1960

 

Les blousons noirs sont un phénomène essentiellement urbain. A Paris chaque porte, chaque quartier prolo possède sa bande. Un article de presse daté de l'été 1959 fait état de six bandes principales à Paris et de 70 autres cliques de moindre importance. (76) Selon la préfecture de police 10000 jeunes fréquentent des bandes dans la capitale. (77)

A l'époque la bande la plus importante de la capitale était celle du Talus capable de regrouper 250 à 300 jeunes le samedi soir. Ceux de la porte de St -Ouen se distinguent par la parfaite maîtrise des diverses langues des voyous. La bande du square des Batignolles et leur chef Pilule sont le sujet d'un reportage de l'émission télé Cinq colonnes à la une en 1960. Tout aussi médiatisée, la bande de la Bastille, forte d'une centaine de membres qui parlait un argot forcé. Une enquête est publiée sur eux l'été 1961 par Christian Magret dans le magazine des têtes couronnées Point de Vue. Le chanteur Moustique membre de ce groupe déclare quelques années plus tard dans un entretien:

" A la fin des années 50, on attaquait un car de flics, on cassait les vitres et on piquait le car pour une virée " (7

La bande du Sactos (Sacré Cœur) tournait aussi autour de la centaine et était protégée par leur curé. Elle était très crainte par les autres bandes. Johnny Hallyday qui faisait partie de la bande du square de la Trinité raconte :

«On jouait les durs. On se battait, mais nous fermions notre gueule lorsque la bande du Sacré-Cœur descendait" (79)

La plupart des bandes se singularisaient en arborant le même signe distinctif, qui allait de la manière de se coiffer, aux différents accessoires ; médailles, voir une tête de mort ou un minuscule couteau retenu au cou par une chaîne, bagues, bracelets ou ceinturons incrustés de pièces de monnaie. Cette singularité se retrouve sur leurs engins à deux roues; mobylettes ou scooters : fanions à tête de mort, hélices en plastique de la même couleur gagnées à la fête foraine. La même décalcomanie collée sur le réservoir ou le garde boue ; photos de Tarzan ou de James Dean, vamp, tête d'indien, trèfle à 4 feuilles. L'accessoire peut donner son nom à la bande, ainsi la bande du Damier d'un port breton arborait un damier sur leurs véhicules.

En 1960, 53 % des jeunes qui fréquentaient les bandes sortaient de familles ouvrières, les fils d'employée représentaient 12%.

A noter que 18 % des effectifs des bandes seraient originaires des milieux sociaux supérieurs.

" La majorité de ces jeunes étaient issue des classes sociales défavorisées bien que la bourgeoisie eut ses blousons dorés. Les bandes constituent une configuration culturelle originale, articulée sur une culture de classe. La culture ouvrière en est le soubassement " (80)

Les adolescents de 15 à 17 ans en constituent le noyau le plus important (53, les plus jeunes de 13 à 14 ans représentent 14,8% des membres et ceux de 18 à 20 ans 18,1 % (81) Les blousons noirs des années 1959-1961 appartiennent à la génération des enfants de la guerre, ceux nées pendant la seconde guerre mondiale entre 1939 et 1945 et dans l'immédiate après guerre.

 

Les bandes tournent généralement autour de trois noyaux. Le noyau central composé de ceux qui étaient le plus en vue, quatre à cinq personnes souvent confrontées à la délinquance. Puis vient la bande proprement dite formée en moyenne d'une quinzaine à une vingtaine de membres qui cherchaient surtout à se faire remarquer. Le troisième noyau qui pouvait être plus important jusqu'à une centaine de jeunes était composé des sympathisants et des postulants qui formaient le halo de la bande présent lors des grandes occasions comme une bagarre entre bandes rivales. La bande forme un milieu homogène, l'embryon en est la "cour " où les enfants d'un même immeuble vivent et grandissent ensemble. Vers l'âge de 12 ans les enfants de plusieurs cours se groupent dans des lieux de rencontre plus vaste : places ou squares où ils se forment en bande. Dans la bande, les adolescents se retrouvent et ne s'expriment qu'en symbiose avec les autres.

Le dynamisme du groupe est contenu dans ses motivations qui portent le jeune à avoir en face de lui des interlocuteurs qui le comprennent, qui ont les même besoins et les mêmes soucis que lui et ne par conséquent être des adultes qu'ils haïssent.

" Les vieux ont s 'en fout, ils peuvent tous crever” répond spontanément un jeune blouson noir au juge d'instruction qui lui parlait de ses parents (82).

Pour son reportage dans l'Express, Jean Cau demande à Jojo de la bande de la Porte de Vanves. " Pourquoi "les vieux" à ton avis ne vous comprennent pas ? " réponse de Jojo : " Parce que qu'on voit la vie autrement ! " " Qu'est ce que tu veux dire ? " lui demande alors l'écrivain. Le blond répond à sa place : " Ils voudraient qu'on porte des gilets, qu'on ait des pantalons comme ça, qu'on soit comme eux ! " (83)

Ensemble, ils reconnaissent être différents des autres, mais cette différence, paradoxalement se manifeste par le maximum de conformité avec ceux du groupe. C'est pour cela que le vêtement, la coupe de cheveux, le langage ont une telle importance, ils manifestent une singularité collective. Mais si la panoplie marque la rupture avec le monde adulte, elle ne devait pas être usurpée. Il faut être reconnu par ses pairs, il y a des modèles, l'orgueil, l'honneur et l'exploit ont une grande place dans la vie des bandes. L'intégration dans une bande n'est pas une chose facile. La bande est une société tellement fermée qu'y pénétrer est incontestablement une victoire. Elle passe par deux étapes, celle de la reconnaissance puis celle de l'acceptation. Pour être accepté, il y a des rites d'admissions. Le postulant doit faire ses preuves en réalisant divers exploits qui pouvaient aller du combat au cran d'arrêt à la course de mobylettes dans les sens uniques ou sur les " fortifs " (Certains tronçons des fortifications de 1870 subsistaient encore dans la capitale à la fin des années 50 (84). Parmi les autres exploits couramment pratiqués ; se battre avec le chef ou piquer une nana dans une bande ennemie. Ces pratiques sont souvent associées avec le rituel du " frère de sang " Le chef du gang entaille avec son couteau l'avant bras du postulant, puis fait la même estafilade en forme de croix sur celui du dernier rentré dans le groupe. Il maintient leur deux bras ensemble, unis par le mélange de leur sang, les deux "frères" jurent que jamais ils ne trahiront leurs camarades. Une autre caractéristique de la bande est le vif sentiment de propriété vis à vis de son territoire. Elle a ses lieux de réunion, ses cafés et ses cinémas et n'en change pas et ne tolère pas qu'une autre bande vienne empiéter sa zone, sinon c'est la guerre. Le square, mini espace de verdure apparaît l'endroit idéal pour leurs rassemblements. Là, les garçons discutent ensemble, se racontent des histoires de filles ou de taules souvent exagérées. Ils s'échangent des idées, blaguent, s'amusent, se chamaillent entre eux tout en écoutant de la musique sur un transistor. Dans ce lieu, où ils traînent souvent tard le soir les adolescents éprouvent un sentiment de liberté.La fête foraine est un autre coin qui les attire, et ils aiment se regrouper autour des auto-tamponneuses. Il y règne une certaine ambiance, adossés à la balustrade, ils prennent plaisir à regarder tourner les voitures en écoutant les derniers disques à la mode ou draguer les filles. L'hiver on se met au chaud dans les salles de jeux avec une prédilection pour le flipper. Au Café, ils ne consomment pratiquement pas d'alcool, préférant le diabolo ou le café crème. Paris, connaît l'hiver 1959 la grande vogue du patin à glace. Les patinoires de Saint Didier ou de la " fédé " de Boulogne sont prises d'assaut par des hordes de gamins.

" La fédérale c'est la roue tournante de tous les blousons noirs, on retrouve les copains de tous les quartiers. Il y a des filles, ce n’est pas cher et on s'amuse bien " raconte Pilule chef de la bande des Batignolles (85). Quant au bal, ils y vont très rarement la plupart de ces garçons ne savent pas danser, mais sur place ils aiment bien provoquer des bagarres.

" Le soir d'une fête patronale une quarantaine de jeunes venus de Rouen à scooter, à cyclomoteur ou en taxi, avaient plusieurs fois tenté de pénétrer dans la salle de bal en refusant de payer. L'expulsion par les gendarmes de deux ivrognes leur fournit le prétexte recherché pour passer aux actes de violence. Toute la bande se rua alors sur les représentants de l'ordre et l'un des gendarmes fut roué de coups. Son collègue tira quelques coups en l'air. Ce geste décontenança un temps les agresseurs mais les gendarmes partis, les jeunes gens pénétrèrent en force dans la salle où il brutalisèrent plusieurs danseurs et plusieurs femmes "(86)

Les bandes importantes comportent parfois un tiers de filles. On y trouve souvent des filles garçons qui rêvent d'être des garçons et se conduisent comme tels. Elles revendiquent leur égalité dans les comportements antisociaux et le manifestent notamment par des attitudes de bravades vis à vis de la police lorsque celle-ci intervient. Le journal le Progrès de Lyon raconte le comportement de deux filles membres d'une bande du quartier de Perrache après leur arrestation :

"On reste confondu lorsque l'on sait que ce sont les deux filles qui tinrent tête avec le plus d'aplomb au commissaire et firent preuve d'une inconcevable impolitesse. L'une se contenta de dire : "Je me fous de la police, je me fous de la famille" L'autre, encore plus effronté, n'alla-t-elle pas jusqu'à déclarer : " Parlez moins fort. Vous me faites mal aux oreilles…" (87)Mais la majorité des adolescentes qui fréquentent les bandes peuvent être classées dans la catégorie des "filles-objets" guère respectée qui servent à l'initiation sexuelle des garçons. Elles vont d'un garçon à l'autre, et prennent une sorte de valeur marchande en se faisant échanger pour trois fois rien! Il y aussi les filles attitrées que possèdent les principaux membres de la bande, qui souvent par prudence sont rarement vues par les autres gars. Les filles participent rarement aux délits, mais en sont les complices indirectes en bénéficiant souvent en forme de cadeaux des produits dérobés. Elles aiment se faire conduire dans des véhicules volés, ce qui donne un certain prestige à l'auteur de l'acte délictueux. La délinquance est souvent un moyen de se poser en homme devant la femme pour obtenir ses faveurs. Si quelques séries B américaines de la fin des années cinquante ont fait des gangs de filles l'un de leurs thèmes favoris. L'existence de quelques bandes féminines en France a été confirmée par certains enquêteurs. Lorsque le journal La Montagne évoque une agression commise par une bande de jeunes filles à Caen, on emploie symboliquement le terme de "jupons noirs" : "Les jupons noirs de Caen rouent de coup un Nord-Africain" (8 On note surtout une délinquance féminine opérée en petit groupe dans les grands magasins. Une fille achète un produit pour occuper la vendeuse, une autre fait le guet, tandis que la troisième vole des vêtements ou des aliments. Comme dans l'histoire du film de Marcel Carné " Terrain Vague " on signale des gangs de garçons dirigés par une fille. Exemple, le gang des As une bande délinquante de la région bordelaise qui avait à sa tête Berthe une gamine de 16 ans. (89)

Terrain Vague

Le rapport au travail du blouson noir est complexe. Le gars qui à l'habitude de vivre en bande n'a pas envie de la quitter pour aller bosser, tandis que celui qui travaille de voir ses copains traîner toute la journée lui donne des mauvaises idées et il s'arrête de travailler. Le marché de l'emploi de l'époque le permettant, on travaille selon l'envie ou la nécessité.

" Si le gars travaille, un moment, pendant une semaine ou un ou deux mois, c'est qu'il a besoin d'argent pour s'habiller, pour manger, pour s'acheter une mobylette. Ou bien c'est qu'il s'est produit un renversement moral: son instinct est devenu faible et sa volonté lui a permis de travailler pendant ce temps là " (90)

" Je travaille quand j'ai besoin de fric. S'il me faut une paire de " groles ", je fais la plonge. Si c'est une nécessité plus grave, je me fais embaucher un mois ou deux dans mon métier" . Raconte Guy 18 ans (91)

Les contrats d'apprentissages sont la plupart du temps des contrats pour la forme. Les patrons en profitent pour mal payer les jeunes, mais ils les font travailler comme des ouvriers adultes. En plus, les jeunes apprentis supportent mal les ordres des chefs d'équipes, de ce fait, ils changent régulièrement de métier. Le plus souvent les jeunes des bandes qui travaillent exercent des métiers sans grande qualification comme: télégraphiste, plombier, graisseur. Des métiers où la main d'œuvre est variable qui leur permet de changer de patron, de lieu de travail à leur guise. Lorsqu'on demande à Moustique le benjamin de la bande de la Bastille qui ambitionne de trouver un boulot " pépère " quel genre de travail il aimerait faire, il répond: " Ben : aide routier, livreur en triporteur ou alors être le fils de taulier, avoir une carte de figurant de cinéma ".(92)

 

76 – Philippe Macaigne "Quelques réflexions sur la présentation de la presse écrite des "blousons noirs", in Annales de Vaucresson, N° 2,1964

77 - C.Freinet, « La formation de l’enfance et de la jeunesse », Edition l’école moderne, 1960

78 - Interview Moustique par Christian Victor in Juxe-Box Magazine N° 86, novembre 1994

79 - Interview Johnny Hallyday par Jacques Barsamian in Juke Box Magazine N° 42, novembre 1990

80 - Jean Charles Lagrée in "Les jeunes chantent leurs cultures", page 19,L’Harmattan , 1982

81 - Rapport annuel de l’Education surveillé pour 1960 in "Les bandes d’adolescents","Les classes d'age" page 3 Philippe Robert, Pierre Lascoumes Les éditions ouvrières,Paris 1974

82 - "Les vieux ? qu'ils crèvent ! « Le mal de la jeunesse » ,in Faim & Soif N°33, 7/02/1960

83 - Jean Cau, Les gosses révoltés, l'Express 30 juillet 1959

84 - Long Chris "Johnny", page 17,J'ai Lu N°2380,

85 - "Square des Batignoles" Reportage de Pierre Dumayet, Cinq colonnes à la une,4/11/1960

86 - « Quand la jeunesse faisait peur », Laurent Mucchielli, chercheur au CNRS

87 - "Des blousons noirs sont surpris dans leur repaire par les policier" in Le Progrès de Lyon, 22 mai 1962

88 - La Montagne, 18 juin 1960, Claire Bacher 3Le phénomème bmousons noirs vu par la presse Maitrise faculté de Clermont Ferrant 2000

89 -Philippe Parrot, Monique Gueneau "Le gang des As" in "Les gangs d’adolescents",PUF,1959

90 - in "Cri d'appel d'un blouson noir", page 47, Fayard, 1962

91 - In “tribune libre des jeunes” Cinémonde 16/10/62

92 - in "Les Blousons

 

Blousons noirs. Soixante ans après, l’expression a gardé toute sa force évocatrice, porteuse d’une mythologie cuir mêlant violence et rock’n’roll naissant sur fond de désœuvrement et de misère sociale (ça ne vous rappelle rien ?). Le festival Filmer la musique, que Poptronics suit quotidiennement, y consacre une journée entière avec deux films, une séance de documents d’actualité d’époque et un concert de Magnetix en clôture au Point Ephémère.

1955, « Graine de violence » (« Blackboard Jungle ») sort au cinéma. C’est l’émeute : la jeunesse française découvre en même temps les déhanchements de Presley et le « Rock Around The Clock » de Bill Haley. Les choses ne seront plus tout à fait pareilles : le rock’n’roll vient d’entrer dans la culture populaire hexagonale. Et avec lui, ceux qu’on appelle encore les « tricheurs », d’après le titre du film de Marcel Carné qui sort en 1958, ces jeunes banlieusards des cités qui sortent de terre. Il y a déjà eu quelques gros incidents : à l’été 1955, un concert de Louis Armstrong déclenche une bataille de trois jours dans les rues de Paris, en octobre 1958, le concert de Bill Haley à l’Olympia donne lieu à des débordements : des fauteuils sont détruits par centaines.

  

Mais c’est à l’été 1959 que la France découvre, tétanisée, les blousons noirs. Le 24 juillet, vingt-cinq jeunes de la Porte de Vanves déboulent dans le XVe arrondissement pour affronter la bande du square Saint-Lambert, vêtus de blousons de cuirs, de jeans, et armés de chaînes de vélo. Le lendemain, on se bagarre à Bandol pour une histoire de filles. Quelques jours plus tard, un policier est blessé à Cannes lors d’affrontements avec une bande de Courbevoie. L’affaire fait la Une (« Un agent de police a été sauvagement poignardé par une horde de tricheurs, de blousons noirs »). Les incidents se multiplient tellement (à la sortie de « Jailhouse Rock » en 1960, le cinéma Le Mac Mahon est littéralement pris d’assaut) que le sinistre Maurice Papon, préfet de police de Paris depuis 1958, songe très sérieusement à interdire le rock’n’roll pour préserver la « tranquillité publique ». Cette peur diffuse de la jeunesse, on la retrouve dans les reportages de l’ORTF,

 

Revenir en haut Aller en basDans quel contexte apparaissent les blousons noirs ?

C’est de la délinquance sur fond de rock’n’roll, de guerre d’Algérie et surtout de naissance des cités. A l’époque, face aux barres de Nanterre, La Défense est un immense terrain vague sur lequel seul le Cnit est construit. A peine sortie de terre, cette urbanisation est déjà porteuse de problèmes et provoque désœuvrement, ennui, marginalisation. Il ne fallait pas être visionnaire pour voir que ça allait être le bordel : l’environnement, c’est déjà celui de « Ma 6-t va crack-er ». Cette jeunesse ouvrière qui traîne en bas de ces grandes barres HLM nickel s’emmerde et se radicalise. Les blousons noirs terrorisent les gens, ils niquent toutes les nanas, qui toutes veulent être niquées par eux ! Ils n’ont pas de conscience politique, pas vraiment de conscience sociale non plus, ils sont dans l’énergie brute : ils foutent le bordel et c’est tout.

Quand le mouvement devient-il massif ?

Quand Hallyday débarque, en 1961. C’est un choc. Jusqu’alors, le business de la musique est aux mains de vieux qui se projettent sur les envies des jeunes et suivent les modes. On a affaire à des orchestres de bal qui jouent du twist, quelques mois plus tard ils font du cha-cha ou du calypso. Hallyday, lui, fait de la musique pour les jeunes sans une once de cynisme. Et ça, les kids, ça leur fait péter les plombs. Quand Johnny ou Vince Taylor jouent à l’Olympia au début des années 60, ils cassent tout, ça fait la Une des journaux, avec des slogans choc, ça fait flipper tout le monde car cette expression de la violence des jeunes en groupe est assez nouvelle. Les blousons noirs succèdent en quelque sorte aux apaches du début du siècle, qui eux étaient vraiment dans le banditisme. Là, ce sont des branleurs. C’est assez inédit.

C’est une esthétique aussi...

Oui, les blousons en cuir, les jeans, on est complètement dans le fantasme du motard, de « L’Equipée sauvage ». Brando, avant James Dean, devient une véritable icône de cette jeunesse. Il y a un côté désuet à les revoir aujourd’hui, un mélange de pathétique et de sublime. Le phénomène est assez européen, très présent en Suisse, en Allemagne, mais en France, c’est quelque chose de dur, le cuir, les chaînes, il y a une volonté d’effrayer le bourgeois, de faire peur, un vrai désir de choquer et de provoquer. Aux Etats-Unis, on ne trouve pas tous ces atours, tout cet apparat.

Les blousons noirs disparaissent peu à peu au cours des années 60. C’est la fin du rock’n’roll dans les cités ?

Difficile de dater la fin du mouvement, beaucoup rentrent dans le rang assez vite (selon quelques rares études, plus de la moitié des blousons noirs ont entre 14 et 17 ans, huit sur dix ont moins de vingt ans, ndlr), une petite frange tombe dans la vraie marginalité. Mais le rock ne disparaît pas pour autant du paysage banlieusard. Le rock’n’roll n’a quitté les cités qu’avec l’arrivée du rap. Jusqu’au début des année 80, tout le monde y écoute du rockabilly et du rock’n’roll, qu’on soit blanc, black ou arabe. Gene Vincent est une star des cités. D’ailleurs, ceux qui ont fondé les premiers labels de rap étaient tous d’anciens fans de rockabilly. La naissance des blousons noirs La bande de « Titine » au pied des HLM du Pré-Saint-Gervais. 'agression du jeune Yuriy, en janvier dans le X Ve arrondissement de Paris, a mis en lumière les affrontements entre bandes. Mais à la fin des années 1950 déjà les héritiers des Apaches de la Belle Epoque n’avaient peur de rien ni de personne. Ils aimaient la castagne, les Mobylette et le rock’n’roll. Immersion chez ces petits voyous du Pré-Saint-Gervais, avec le photographe André Lefebvre. La vague est partie des Etats-Unis. Leurs références sont James Dean et sa « Fureur de vivre », Brando dans « L’équipée sauvage ». Partout, ce sont les mêmes jeunes en proie au même mal du siècle. En Angleterre , on les appelle les « Teddy boys », en Allemagne les « Halbstarken », en Suède, les « shunna folke », en France ce sont « les blousons noirs ». L’expression est lancée par le journal « France-Soir », à l’été 1959, après un affrontement entre bandes, square Saint-Lambert, dans le XVe arrondissement de Paris. Avec leurs manteaux de cuir, leurs cheveux mi-longs gominés, leurs chaînes de vélo et leurs poings américains, ils se rassemblent au pied des tours ou des pavillons aux façades décrépies, dans les quartiers populaires des villes ou de leur périphérie. La plupart du temps, les blousons noirs appartiennent à la classe ouvrière, vivent de petits boulots et grandissent dans des familles éclatées. Ils sont les laissés-pour-compte des Trente Glorieuses marquées par l’essor économique et l’émergence de la classe moyenne. Dans le groupe du Pré-Saint-Gervais qu’ont suivi Jean Maquet et André Lefebvre, les journaliste et photographe de Match, la moyenne d’âge est de 16 ans. « Ces jeunes gens sont tout au plus égarés, ils ne sont pas vicieux. Ils vivent en bandes, certes, mais ce mot de bande est trompeur. On pense aux bandes de gangsters, écrit Jean Maquet [...]. Les membres des bandes de blousons noirs, dans l’immense majorité des cas, ne sont que des copains. Il faut insister sur ce point. Il serait on ne peut plus néfaste, et pour tout le monde, que le public se fasse du blouson noir une idée trop noire [...]. Le problème des blousons noirs est grave : il n’est pas encore tragique. » Des copains qui inventent leur propre culture, de nouveaux codes.

Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes @ Sur leurs postes de radio, ils écoutent le rock’n’roll d’Elvis Presley ou de Vince Taylor. Très loin des yéyés. « Ils ont besoin de se sentir virils », écrivait le journaliste de Match. « Cela donne la baston, c’est-à-dire le règlement de comptes à mains nues entre hommes, et, de temps en temps, la “frite”, c’est-à-dire la bagarre générale [...]. Bref, la violence. » Une violence gratuite, pour passer le temps, par exubérance juvénile, par désir de se montrer brave. On se bat pour s’imposer, prendre le pouvoir dans le quartier ou juste pour la gloire, on se tape des virées dans des voitures volées… Ils commettent des larcins, pillent ou cassent plus par défi que par besoin ou conviction. Et, s’ils brandissent leur haine des « flics » et de l’ordre bourgeois, ils ne défendent aucune cause. Leur conscience politique ne ressemble en rien à celle des étudiants de Mai 1968 qui crieront leur révolte quelques années plus tard. Malgré leur rejet de l’autorité, les bandes sont hiérarchisées autour du chef et de ses lieutenants, qui ont tous un surnom. Pour en être, il faut respecter certains rituels, être initié, savoir se montrer téméraire, commettre un vol ou se mesurer à un rival. La presse, qui s’est emparée du phénomène, en fait un mythe. Un congrès sur la délinquance juvénile est même organisé en Italie. Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes. Parmi eux, 45 000 ont moins de 18 ans. Comme les loubards ou les jeunes des cités après eux, ils veulent s’affirmer, interroger la société, la provoquer, mettre à l’épreuve sa capacité à les intégrer. En marge, cette jeunesse défavorisée est gangrenée par le désœuvrement. « Sur ce point, ils sont unanimes. Ils s’ennuient, écrivait Jean Maquet. Ils sont incapables de rester seuls. La bande, cette bande fluctuante, c’est ce qui les délivre de leur solitude, leur donne l’illusion d’une fraternité et sans doute, pour beaucoup d’entre eux, d’une famille. Ils ne lui en demandent pas plus. » 69 VENISSIEUX Les MJC 1959-1981 De l'été des blousons noirs à l'été des Minguettes Broché – 3 avril 2008 Les Maisons des jeunes et de la culture (MJC) font partie de ces institutions méconnues bien que souvent évoquées. Parfois confondues avec les Maisons de la culture d'André Malraux, parfois assimilées à de simples maisons de jeunes, elles sont victimes de l'ampleur de leur objectif : lier jeunesse et culture dans une perspective d'éducation populaire. Ce livre retrace leur histoire à leur apogée, entre 1959, lorsque la médiatisation du phénomène blousons noirs favorise une mobilisation en leur faveur, et 1981, quand l'apparition du " mal des banlieues " signalait un changement d'époque : l'insertion sociale des jeunes devenait une priorité tandis que le lien entre jeunesse, loisirs et action culturelle achevait de se dissoudre dans la crise du socio-culturel. Entre ces deux dates, le millier de MJC que comptait alors le territoire a connu une histoire aussi riche que mouvementée. La diversité des activités abritées dans leurs murs n'a d'ailleurs pu que contribuer à rendre les MJC difficilement saisissables : tour à tour foyers de jeunes et maisons pour tous, proposant expérimentations théâtrales et ateliers de bricolage, espaces de débats et sociabilité, elles furent aussi des pépinières pour la formation de militants culturels et politiques locaux. Lieux singuliers qui ont pu être présentés, parfois simultanément, comme des repaires de gauchistes, des centres de propagande communiste et des terreaux de la deuxième gauche, les MJC permettent de saisir la complexité de la vie associative, dans sa richesse mais aussi sa difficulté. Voilà un très beau livre de synthèse sur un sujet qui ne peut manquer d’intéresser les lecteurs de cette revue. Même si les MJC (Maisons des jeunes et de la culture) n’avaient pas pour finalité de contribuer à la lutte contre la délinquance, elles ont été parfois perçues par les municipalités comme un des outils efficaces de prévention, en particulier à l’époque des blousons noirs. Le sous-titre adopté par l’ouvrage rappelle d’ailleurs cet impact possible ou souhaité sur la prévention. Mais Laurent Besse a bien d’autres ambitions ici, et il analyse les MJC à l’aune de l’éducation populaire, et de ses grandes ambitions au lendemain de la Libération. Il les suit donc depuis la République des jeunes, dont l’idée est née au sein du gouvernement de la France libre à Alger (d’après leur fondateur André Philip), jusqu’à l’arrivée de la gauche au pouvoir. En fait, il commence surtout avec leur très forte expansion sous le régime gaulliste avec la nomination de Maurice Herzog, fin 1958, comme haut-commissaire à la Jeunesse et aux Sports. La préface d’Antoine Prost souligne d’ailleurs le paradoxe des MJC : ce sont des institutions de gauche surtout présentes dans les villes de droite et du centre, et Laurent Besse montre que les MJC bénéficient avec Herzog d’un appui essentiel. En 1965, lors de l’anniversaire de leurs vingt ans, la fédération des MJC compte trois fois plus de maisons qu’en 1959. Deux autres paradoxes, soulignés par Antoine Prost, caractérisent les MJC. Elles sont laïques, mais mal vues de la Ligue de l’enseignement. Elles sont destinées aux jeunes, mais accueillent bien d’autres classes d’âge.

2Issu d’une thèse soutenue à Paris-I en 2004, ce livre repose sur une abondante documentation, permettant d’analyser les réactions du tissu local comme les enjeux nationaux, la sociologie des directeurs autant que la philosophie des fondateurs, les pratiques de loisirs autant que les ambitions culturelles. Si les archives de la fédération FFMJC (Fédération française des maisons de jeunes et de la culture), et de la fédération concurrente UNIREG (Union des fédérations régionales de MJC) à partir de 1969, ont été essentielles, elles ont été heureusement complétées par celles des douze principales fédérations régionales, et celles des MJC de quelques grandes villes (Châtellerault, Grenoble, Orléans) ainsi que de fonds privés de militants. L’ouvrage est donc parfaitement étayé, foisonnant de précisions qui en rendent la lecture vivante, et qui n’effacent jamais le souci d’une réflexion synthétique.

3Le livre est bâti sur une chronologie fine, qui distingue trois périodes au cours de ces deux décennies, qui ont vu la multiplication des MJC et leur ouverture à un public élargi. Les 14-21 ans y sont majoritaires dans la décennie 1960 (cf. la première partie « Des maisons pour les jeunes - 1959-1965 »), recrutés parmi les « inorganisés », qui n’appartiennent à aucun mouvement, et dont on souhaite qu’ils viennent aussi bien du monde des ouvriers (les travailleurs manuels), que des étudiants (les lycéens). Le projet des initiateurs des MJC (et l’auteur insiste sur le portrait d’André Philip et de sa philosophie de laïcité ouverte) est d’ouvrir une maison de loisirs culturels et éducatifs pour cette classe d’âge, tous milieux sociaux confondus. Le pari est tenu, en particulier autour des activités de ping-pong et de judo.

4La deuxième partie (« Maisons contestées ? Maisons de la contestation ? 1966-1969 ») insiste sur le choc qu’a été pour la fédération des MJC le départ de Maurice Herzog et son remplacement par François Misoffe, devenu ministre de la Jeunesse et des Sports, hostile aux animateurs et décidé à étouffer ces maisons de la contestation et à les remplacer par « mille clubs » beaucoup plus légers. La fédération est déstabilisée et même si le projet ministériel de suppression de la FFMJC échoue, André Philip démissionne. La FFMJC a fait figure d’administration parallèle et cela ne pouvait pas laisser le pouvoir gaulliste indifférent. C’est le moment aussi où les MJC s’ouvrent aux débats et, sans être le fer de lance de la contestation en 1968, s’en font la caisse de résonance.

5L’interrogation sur « Des maisons pour tous (1970-1971) » qui structure la dernière partie, repose sur le fait que les MJC accueillent alors un public nouveau, de femmes et d’enfants, relativement inconnu jusqu’ici, que l’animateur militant laisse la place peu à peu aux vacataires compétents. Elles deviennent des maisons de loisirs pour tous, et des lieux d’une autre culture, avec multiplication de débats sur les marges et les luttes de tous les peuples. Elles accueillent des chanteurs compositeurs débutants et créent des spectacles appelés à circuler. À la fin des années 1970, la mise en cause du socioculturel est l’enjeu de débats passionnés, et le développement de la crise amorce la réflexion sur l’insertion économique des jeunes autant que sur leur développement culturel. Mais les MJC ne sont pas les seules sur ce terrain…

6Tout au long de l’ouvrage est tenu le fil de la réflexion sur l’éducation populaire, sur ses objectifs, ses contenus, depuis l’ambition des origines, jusqu’aux crises mettant en cause la survie même des MJC, aux prises avec les politiques locales et nationales. Comment développer l’éducation populaire ? Comment intégrer ceux qui refusent la participation régulière aux ateliers, préférant les rencontres informelles du foyer autour du baby-foot ? Comment faire coexister les « intellectuels » avec les autres ? Comment, sans exclure, désamorcer les agressivités, les déprédations ? Le livre aborde l’émergence du métier d’éducateur, qui s’est faite précisément au sein des MJC, dans un milieu qui a longtemps préféré le terme de « directeur » (même en pleine affirmation de la non-directivité des années post 68) à celui d’animateur. Comment les recruter, comment les former ? Il insiste sur le fait que les MJC ont été des équipements discrets, à la différence des maisons de la culture, qui, par comparaison, s’affirmaient dans le paysage urbain comme temples de la culture.

7L’analyse culturelle est étroitement imbriquée dans l’analyse des politiques nationales de la jeunesse, mais aussi des politiques locales. La position originale des MJC qui sont des associations 1901 cogérées avec les municipalités, si elle fournit une initiation à la vie démocratique, est aussi source de conflits avec les municipalités. La place du parti communiste, souvent surestimée, fait des MJC des lieux inquiétants pour les élus de la droite, bien que certains, dans bien des villes, leur soient restés fidèles, sensibles à la qualité de leur travail. La comparaison avec les centres sociaux, beaucoup plus marqués par les militants JOC, en fait ressortir la spécificité essentielle dans une jolie formule. Pour Laurent Besse, le centre social, c’est « l’espace des poussettes », alors que la MJC est « l’espace des mobylettes ».

8La conclusion de Laurent Besse est sévère. Pour lui, l’action des MJC se solde par un relatif échec, dans la mesure où elles n’ont pas été capables de s’adresser en masse aux jeunes. Certes, elles ont été les fruits d’une très grande ambition qui aurait pu faire d’elles, sous la IVe République, ce que les maisons d’école avaient été à la IIIe, et des éducateurs populaires, les nouveaux instituteurs de la République. Certes, elles ont bénéficié de la crise des mouvements d’action catholique. Néanmoins, leur projet de devenir le banc d’essai de la citoyenneté, d’être écoles de la démocratie, n’a pas abouti. L’auteur souligne cependant l’offre qu’elles ont apportée à nombre de petites villes et de villes de banlieue, qui seraient restées des déserts culturels sans elles. Mais leur humanisme polyvalent, qui voulait que l’homme complet soit initié à toutes les disciplines, a cédé devant la spécialisation de la vie associative. En outre à la fin des années 1970, l’heure n’était plus à l’animation, mais à l’insertion professionnelle des jeunes. Et Laurent Besse de conclure sur les difficultés actuelles des MJC, à replacer dans « le contexte de déclin de la ferveur éducative, peut-être de l’utopie éducative ».

Haut de page

Pour citer cet article

Référence papier

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière », 12 | 2010, 256-259.

Référence électronique

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière » [En ligne], 12 | 2010, mis en ligne le 21 juin 2012, consulté le 27 juin 2021. URL : journals.openedition.org/rhei/3212 ; DOI : doi.org/10.4000/rhei.3212

Haut de page

Auteur

Dominique Dessertine

Articles du même auteur

Histoire de l’éducation populaire (1815-1945). Perspectives françaises et internationales [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 22 | 2020

Ces êtres intéressants et infortunés : les enfants trouvés des Basses-Alpes au XIXe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 20 | 2018

Droits des enfants au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 19 | 2017

L’œuvre de secours aux enfants et les populations juives au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 18 | 2016

Jean-Pierre Méric, Les pionniers de Saint-Sauveur : la colonie agricole du Médoc pour les enfants trouvés (1844-1869) [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 16 | 2014

(Lecture de) Des enfants venus de loin. Histoire de l’adoption internationale en France [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 15 | 2013

Tous les textes...

Ebola virus (EBOV, formerly designated Zaire ebolavirus) is the sole member of the Zaire ebolavirus species, and the most dangerous of the five known viruses within the genus Ebolavirus.[1] Four of the five known ebolaviruses cause a severe and often fatal hemorrhagic fever in humans and other primates, known as Ebola virus disease. The virus and its species were both originally named for Zaire (now the Democratic Republic of Congo), the country where it was first described,[1] and was at first suspected to be a new "strain" of the closely related Marburg virus;[2][3] the virus (but not its species) was renamed to "Ebola virus" in 2010 to avoid confusion. The species is a virological taxon species included in the genus Ebolavirus, family Filoviridae (whose members are called Filovirus[4]), order Mononegavirales.[1] The Zaire ebolavirus species is also the type species (reference or example species) for ebolavirus. Its natural reservoir is believed to be bats, particularly fruit bats, and it is primarily transmitted between humans and from animals to humans, through body fluids.

 

The EBOV genome is approximately 19,000 base pairs long. It encodes seven structural proteins: nucleoprotein (NP), polymerase cofactor (VP35), (VP40), GP, transcription activator (VP30), VP24, and RNA polymerase (L).[5] Its is difficult to study due to the virulent nature of the virus.

 

Because of its high mortality rate, EBOV is also listed a select agent, World Health Organization Risk Group 4 Pathogen (requiring Biosafety Level 4-equivalent containment), a U.S. National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, U.S. CDC Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group.

EBOV carries a negative-sense RNA genome in virions that are cylindrical/tubular, and contain viral envelope, matrix, and nucleocapsid components. The overall cylinders are generally approx. 80 nm in diameter, and having a virally encoded glycoprotein (GP) projecting as 7-10 nm long spikes from its lipid bilayer surface.[6][not specific enough to verify] The cylinders are of variable length, typically 800 nm, but sometimes up to 1000 nm long. The outer viral envelope of the virion is derived by budding from domains of host cell membrane into which the GP spikes have been inserted during their biosynthesis.[citation needed] Individual GP molecules appear with spacings of about 10 nm.[citation needed] Viral proteins VP40 and VP24 are located between the envelope and the nucleocapsid (see following), in the matrix space.[7] At the center of the virion structure is the nucleocapsid, which is composed of a series of viral proteins attached to a 18–19 kb linear, negative-sense RNA without 3′-polyadenylation or 5′-capping (see following);[citation needed] the RNA is helically wound and complexed with the NP, VP35, VP30, and L proteins;[8][better source needed] this helix has a diameter of 80 nm and contains a central channel of 20–30 nm in diameter.

 

The overall shape of the virions after purification and visualization (e.g., by ultracentrifugation and electron microscopy, respectively) varies considerably; simple cylinders are far less prevalent than structures showing reversed direction, branches, and loops (i.e., U-, shepherd's crook-, 9- or eye bolt-shapes, or other or circular/coiled appearances), the origin of which may be in the laboratory techniques applied.[9] The characteristic "threadlike" structure is, however, a more general morphologic characteristic of filoviruses (alongside their GP-decorated viral envelope, RNA nucleocapsid, etc.)

Each virion contains one molecule of linear, single-stranded, negative-sense RNA, 18,959 to 18,961 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are sufficient for replication.[9] It codes for seven structural proteins and one non-structural protein. The gene order is 3′ – leader – NP – VP35 – VP40 – GP/sGP – VP30 – VP24 – L – trailer – 5′; with the leader and trailer being non-transcribed regions, which carry important signals to control transcription, replication, and packaging of the viral genomes into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs because it is a negative sense RNA virus, as well as for replication of the viral genome. Sections of the NP and the L genes from filoviruses have been identified as endogenous in the genomes of several groups of small mammals.[10]

There are two candidates for host cell entry proteins. The first is the host-encoded Niemann–Pick C1 (NPC1), a cholesterol transporter protein, appears to be essential for entry of Ebola virions into the host cell, and for its ultimate replication.[11][12] In one study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse-adapted Ebola virus.[ambiguous][jargon][11] In another study, small molecules were shown to inhibit Ebola virus infection by preventing viral envelope glycoprotein (GP) from binding to NPC1.[12][13] Hence, NPC1 was shown to be critical to entry of this filovirus, because it mediates infection by binding directly to viral GP.[12]

 

When cells from Niemann Pick Type C patients lacking this transporter were exposed to Ebola virus in the laboratory, the cells survived and appeared impervious to the virus, further indicating that Ebola relies on NPC1 to enter cells;[citation needed] mutations in the NPC1 gene in humans were conjectured as a possible mode to make some individuals resistant to this deadly viral disease.[citation needed][speculation?] The same studies[which?] described similar results regarding NPC1's role in virus entry for Marburg virus, a related filovirus. A further study has also presented evidence that NPC1 is critical receptor mediating Ebola infection via its direct binding to the viral GP, and that it is the second "lysosomal" domain of NPC1 that mediates this binding.[14]

 

The second candidate is TIM-1 (aka HAVCR1).[15] TIM-1 was shown to bind to the receptor binding domain of the EBOV glycoprotein, to increase the receptivity of Vero cells. Silencing its effect with siRNA prevented infection of Vero cells. TIM1 is expressed in tissues known to be seriously impacted by EBOV lysis (trachea, cornea, and conjunctiva). A monoclonal antibody against the IgV domain of TIM-1, ARD5, blocked EBOV binding and infection.

 

Together, these studies suggest NPC1 and TIM-1 may be potential therapeutic targets for an Ebola anti-viral drug and as a basis for a rapid field diagnostic assay.

Being acellular, viruses such as Ebola do not replicate through any type of cell division; rather, they use a combination of host- and virally encoded enzymes, alongside host cell structures, to produce multiple copies of themselves; these then self-assemble into viral macromolecular structures in the host cell.[8][better source needed] The virus completes a set of steps when infecting each individual cell:[citation needed]

 

The virus begins its attack by attaching to host receptors through the glycoprotein (GP) surface peplomer and is endocytosed into macropinosomes in the host cell.[16][non-primary source needed] To penetrate the cell, the viral membrane fuses with vesicle membrane, and the nucleocapsid is released into the cytoplasm. Encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3'-5') of polyadenylated, monocistronic mRNAs[jargon] and, using the host cell's ribosomes, tRNA molecules, etc., the mRNA is translated into individual viral proteins.

 

These viral proteins are processed, a glycoprotein precursor (GP0) is cleaved to GP1 and GP2, which are then heavily glycosylated using cellular enzymes and substrates. These two molecules assemble, first into heterodimers, and then into trimers to give the surface peplomers. Secreted glycoprotein (sGP) precursor is cleaved to sGP and delta peptide, both of which are released from the cell.[citation needed] As viral protein levels rise, a switch occurs from translation to replication. Using the negative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly encapsidated.

 

The newly formed nucleocapsids and envelope proteins associate at the host cell's plasma membrane; budding occurs, destroying the cell.

Ebolavirus is a zoonotic pathogen. Intermediary hosts have been reported to be "various species of fruit bats [...] throughout central and sub-Saharan Africa", but infection in bats has not been proven yet.[17] End hosts are humans and great apes, infected through bat contact or through other end hosts. Pigs on the Philippine islands have been reported to be infected with Restonvirus, so other interim or amplifying hosts may exist.[17]

Ebola virus is one of the four ebolaviruses known to cause disease in humans. It has the highest case-fatality rate of these ebolaviruses, averaging 83% since first described in 1976, although fatality rates up to 90% have been recorded in one epidemic (2002–03). There have also been more outbreaks of ebola virus than of any other ebolavirus. The first outbreak occurred on 26 August 1976 in Yambuku.[18] The first recorded case was Mabalo Lokela, a 44‑year-old schoolteacher. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact.

Zaire ebolavirus is pronounced /zɑːˈɪər iːˈboʊləvaɪərəs/ (zah-eer ee-boh-lə-vy-rəs). Strictly speaking, the pronunciation of "Ebola virus" (/iːˌboʊlə ˈvaɪərəs/) should be distinct from that of the genus-level taxonomic designation "ebolavirus/Ebolavirus/ebolavirus", as "Ebola" is named for the tributary of the Congo River that is pronounced "Ébola" in French,[19] whereas "ebola-virus" is an "artificial contraction" of the words "Ebola" and "virus," written without a diacritical mark for ease of use by scientific databases and English speakers. According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Zaire ebolavirus is always to be capitalized, italicized, and to be preceded by the word "species". The names of its members (Zaire ebolaviruses) are to be capitalized, are not italicized, and used without articles.[1]

 

Ebola virus (abbreviated EBOV) was first described in 1976.[2][3][20] Today, the International Committee on Taxonomy of Viruses lists the virus as the single member of the species Zaire ebolavirus, which is included into the genus Ebolavirus, family Filoviridae, order Mononegavirales. The name Ebola virus is derived from the Ebola River — a river that was at first thought to be in close proximity to the area in Democratic Republic of Congo, previously called Zaire, where the first recorded Ebola virus disease outbreak occurred — and the taxonomic suffix virus.[1]

 

The species was introduced in 1998 as Zaire Ebola virus.[21][22] In 2002, the name was changed to Zaire ebolavirus.[23][24

Ebola virus was first introduced as a possible new "strain" of Marburg virus in 1977 by two different research teams.[2][3] At the same time, a third team introduced the name Ebola virus.[20] In 2000, the virus name was changed to Zaire Ebola virus,[25][26] and in 2002 to Zaire ebolavirus.[23][24] However, most scientific articles continued to refer to Ebola virus or used the terms Ebola virus and Zaire ebolavirus in parallel. Consequently, in 2010, the name Ebola virus was reinstated.[1] Previous abbreviations for the virus were EBOV-Z (for Ebola virus Zaire) and most recently ZEBOV (for Zaire Ebola virus or Zaire ebolavirus). In 2010, EBOV was reinstated as the abbreviation for the virus.

To be considered a member of the species Zaire ebolavirus, a virus of the genus Ebolavirus is required to fulfill certain requirements:[1]

 

it is found in the Democratic Republic of the Congo, Gabon, or the Republic of the Congo

it has a genome with two or three gene overlaps (VP35/VP40, GP/VP30, VP24/L)

it has a genomic sequence that differs from the type virus by less than 30%

Furthermore, the virus' genome cannot diverge from that of the variant Mayinga (EBOV/May) by more than 10% at the nucleotide level for it to be considered an Ebola virus.[1]

Staphylococcus saprophyticus growing on ChromID CPS chromogenic agar. Isolate from a urine from a 21 year old pregnant female with proteinuria and a high urinary leucocyte count. Isolate appears very pale pink on this medium

Female marbled salamanders (Ambystoma opacum) make nests along the margins of dry seasonal ponds by excavating shallow depressions below the leaf litter. After laying 50-200 eggs, female A. opacum often stay with their clutches, sometimes rotating or moving the eggs. This brooding behavior is thought to protect eggs from desiccation, predators, and fungal pathogens. Females may brood eggs for several months, depending how long it takes ponds to fill. Although eggs may develop to hatching stage in 9-15 days, hatching only occurs once eggs are inundated.

 

Leon Co., FL

  

www.zacharycava.net

Examining the Effectiveness of Biologicals Against Downy Mildew in Grapes www.growingproduce.com/fruits/grapes/examining-the-effect...

Downy mildew is a challenge for all grape growers, especially on the East Coast where the disease can strike when conditions are wet, particularly when rains occur with temperatures ranging from the 60s to low 80s (°F). The pathogen for downy mildew can spread rapidly. It takes only four to six days from one round of infection until a second-generation of spores develops and new infections occur. This pathogen is one that all Vitis vinifera cultivars are highly susceptible to, as are certain hybrid and native cultivars.

 

“Susceptible cultivars require some sort of a spray program in Eastern climates,” says Wayne Wilcox, Professor of Plant Pathology and Plant-Microbe Biology at Cornell University. “The required intensity of the spray program is determined by the cultivar’s inherent level of susceptibility, weather conditions during the growing season, and the degree to which effective cultural practices are used.”

 

While sustainability has become a major push among winegrape growing regions out West, it’s only natural to see how their Eastern compatriots would be interested in pursuing similar goals. Growers and Cornell Cooperative Extension developed a voluntary self-assessment sustainability program called VineBalance.

 

On Long Island, this has been expanded to a program where growers use a third-party inspector to verify that the vineyard meets the program requirements. So, using more sustainable disease control products is a natural necessity. The trouble is, with wet growing conditions and the high probability of downy mildew, this can be a challenge for growers to achieve.

 

“Effective biocontrol products certainly fit within any sustainability push, since they help to promote the goals. But since one of the pillars of sustainability is ‘economic,’ the products must be effective,” he says. “Because the choice of effective biocontrol materials is rather limited, we’re always looking for something else to supplement what’s available now. Beyond that, a lot of growers would like to be as “green” as they can while still protecting their crop effectively, whether they are part of a formal ‘sustainable’ program or not.”

 

Studying Biologicals for Control

Wilcox has been working with several biological products to study their effectiveness against downy mildew. This includes LifeGard WG, distributed by Certis. Wilcox studied the use of Lifeguard on ‘Chardonnay,’ a highly-susceptible Vitis vinifera cultivar.

 

He compared the results of the vines treated with LifeGard to untreated vines and vines treated with conventional materials. Although he got excellent results in the first year of studying, Wilcox accidentally used a higher application rate of LifeGard. But, in the second year of the study and with the right application rate, Wilcox still saw excellent results.

 

“Disease pressure was almost as high in 2015, and LifeGard again provided control comparable to the best conventional materials, using the correct rate this time,” he says. “We had a drought in 2016 with very little downy mildew developing, so the results from last year didn’t tell us much.”

 

Expanding the Scope

This year, Wilcox will be looking at the efficacy of several biological products against downy mildew, powdery mildew, Botrytis bunch rot, and sour rot. His research will again include LifeGard’s effectiveness against downy mildew. He says the mechanism that is claimed to provide LifeGard’s activity is a promotion of the plant’s natural resistance to diseases, so he’s also looking to expand the research to examine LifeGard’s efficacy against other grape diseases.

 

An important difference, Wilcox says, between his trials and application to a typical commercial vineyard is he targets the most susceptible cultivars and high inoculum pressure.

 

“This does allow us to distinguish between stronger and less-strong materials. However, some of the ‘weaker’ materials look worse than they would in many commercial settings where inoculum carryover from one year to the next is relatively low and there are no unsprayed vines scattered throughout the vineyard from which disease can easily spread.”

 

What Else Can Growers Do

Wilcox suggests growers be mindful about site selection and canopy management as non-chemical ways to help control disease. He suggests management practices that promote drying of fruit and foliage can help reduce disease pressure.

 

For those growers interested in sustainability, Wilcox says there are a few newer biological products that look promising, in addition to some of the greener conventional options. He also says that sustainable and organic approaches should view sprays as supplementing cultural control practices. But, above all he says growers, especially organic winegrape growers, should consider the susceptibility of cultivars prior to planting. “There’s not a lot of meaningful difference among cultivars if they are committed to growing vinifera grapes, but there are huge differences among hybrids and natives,” he says. “If some of the relatively resistant cultivars in these groups will suit the business plan, this is the first, and often most effective,

 

“There’s not a lot of meaningful difference among cultivars if they are committed to growing vinifera grapes, but there are huge differences among hybrids and natives,” he says. “If some of the relatively resistant cultivars in these groups will suit the business plan, this is the first, and often most effective, line of defense.”

 

www.growingproduce.com/fruits/grapes/examining-the-effect...

  

I photographed many wild macaque monkeys whilst out trekking in Black River Gorges National Park. I found them fascinating and could watch them all day long. So many of their characteristics are so human like, I especially found their facial expressions so endearing.

 

This one had been raiding the bins near the carpark and had found something, that by the looks of it, he didn't like! LOL

 

The Mauritian crab-eating macaque (Macaca fascicularis) monkey also known as the long-tailed macaque, are a cercopithecine primate native to Southeast Asia. They originate from South West Asia (Java and/or Malaysia and/or Indonesia) and were introduced by Dutch sailors during the XVIII century. Even the founder population was limited to a few individuals, it rapidly grew after introduction and is now considered as a threat for endemic ecosystems and native fauna and flora species. The current wild population has been estimated to be between 40,000 to 60,000 individuals.

 

The crab-eating macaque lives in matrilineal social groups with a female dominance hierarchy, and male members leave the group when they reach puberty. They are opportunistic omnivores and have been documented using tools to obtain food in Thailand and Myanmar.

 

It is referred to as the cynomolgus monkey in laboratories. The small size of original population, its absence of pathogens and the insular nature of Mauritius gifted the Mauritian Cynomolgus with exceptional advantages for biomedical research, despite of the fact that the colony was originally constituted from wild monkeys.

First submission to the group. An unfortunate fly found today at Magor marsh SSSI that has been killed by an entomopathgenic (insect-killing) fungus. The fungus gets into the insect and then grows, eventually causing it to seek out the tops of plant stems, where it clings on fast, and dies. The fungus then bursts through the body wall and releases spores, which because the insect is high up get carried away on the breeze to seek new hosts.

The Gram-positive bacteria Staphylococcus epidermidis and Staphylococcus aureus are the most common pathogens in hospital-acquired infections. The costs related to infections caused by these strains in the hospital setting are enormous and represent a major healthcare burden. Furthermore, the more recent combination of extraordinary virulence and multiple antibiotic resistance in community-acquired methicillin-resistant strains of S. aureus (CA-MRSA) poses an additional severe threat to public health.

 

S. aureus may cause a multitude of serious infections, including toxic shock and scalded skin syndromes, endocarditis, and pneumonia, to name but a few. In contrast, infections with S. epidermidis are usually chronic and less severe. The most important type of disease caused by S. epidermidis is the colonization and infection of indwelling medical devices.

 

The outcome of infections with S. epidermidis and S. aureus is closely linked to their interaction with human host defenses. Thus, mechanisms of immune evasion such as the formation of biofilms represent significant virulence determinants in chronic infections with staphylococci.

 

Credit: Michael Otto, Ph.D.

More about Michael Otto, Ph.D. and his work. (http://www.niaid.nih.gov/labsandresources/labs/aboutlabs/lhbp/pathogenmoleculargeneticssection/Pages/otto.aspx)

 

www.microbeworld.org

Vanjie Alocilja, AgBioResearch scientist and professor of Biosystems and Agricultural Engineering, is working on biosensors that can detect dangerous pathogens.

 

Alocilja works at the nano level using extremely tiny nanoparticles, nanotubes, nanomagnets, and nanopores to build her sensors.

Les blousons noirs sont une sous-culture juvénile apparue en France dans les années 1950 et qui a connu son apogée entre 1958 et 1961. Issue de l'influence américaine, connotée à un code vestimentaire particulier et au rock'n roll, elle a été la matrice originelle du mouvement yéyé et de quasiment toutes les modes adolescentes ultérieures. Des sous-cultures similaires ont fleuri au même moment dans d'autres pays d'Europe.

La culture « blouson noir » s'est cristallisée autour d'importations américaines qui ont été autant de chocs culturels :

Le film L'Équipée sauvage (The Wild One), sorti en 1953 aux États-Unis mais popularisé courant 1955 en Europe, où le personnage interprété par Marlon Brando révèle d'un coup une façon d'être qui fait époque : cuir noir, moto, machisme, volonté de choquer, esprit de gang, violence à la limite de la criminalité.

Un autre film, La Fureur de vivre (Rebel Without a Cause) arrive en 1956 en France et fait de James Dean une icône définitive. Il introduit l'idée importante que le comportement des (futurs) blousons noirs n'est pas seulement un choix délibéré mais procède d'une fatalité générationnelle et de l'incompréhension des adultes.

L'arrivée au même moment du rock'n roll (Bill Haley et Elvis Presley en premier lieu, puis Gene Vincent, Eddie Cochran etc.) ajoute le son à l'image. Mais c'est une chanteuse française a priori non associée au rock'n roll qui apporte en 1956 une énorme visibilité médiatique au phénomène en formation, Édith Piaf, avec la chanson L'Homme à la moto, indirectement inspirée par L'Équipée sauvage.C'est durant l'été 1959 que l'appellation « blousons noirs » apparaît pour la première fois dans la presse, avec un article de France-Soir du 27 juillet 1959 relatant un affrontement entre bandes survenu au Square Saint-Lambert, dans le XVe arrondissement de Paris[1]. Cette désignation s'impose soudain comme synonyme de « jeunes voyous ». Les journaux se mettent alors à surenchérir en évoquant des bandes caractérisées par leur taille importante (il est question de groupes comptant jusqu'à une centaine de jeunes) et par leur violence. Les « blousons noirs » sont décrits comme des asociaux qui se battent à coups de chaînes de vélo (ou de moto), de coups de poing américains voire de couteaux à cran d'arrêt, qui cherchent la bagarre pour défendre leurs territoires urbains, particulièrement autour des portes de Paris, ou en faisant des descentes dans des bals ou des fêtes.Peu après, les journalistes forgèrent le terme « blousons dorés » pour désigner les jeunes fils de la bourgeoisie qui se faisaient remarquer dans les faits divers, par opposition aux « blousons noirs » qui étaient plutôt issus de milieux populaires.

Cette campagne de presse, qui tourne à la psychose collective, aura pour principal effet de mettre en vogue le genre blouson noir. Autour de 1960, dans tout le pays et dans tous les milieux sociaux, les jeunes gens à la mode aiment à s'habiller de cuir (mais le véritable Perfecto est encore rarissime), portent de grosses chemises à carreaux, se coiffent en arrière avec au sommet du front une large boucle asymétrique souvent brillantinée (la célèbre « banane »). À défaut d'une véritable moto, luxe accessible seulement aux plus fortunés, on roule sur des cyclomoteurs qui en ont à peu près l'aspect, de préférence une Flandria ou une Paloma, une mobylette à la rigueur. La petite délinquance est répandue dans ce milieu, sans être généralisée. Mais afin de choquer, les blousons noirs (qui se nomment eux-mêmes « loulous ») affectent de jouer les durs et de parler des argots empruntés au monde des truands.Ce milieu fournit la base sociale qui sera le marché initial du rock français. Il trouve ses héros en Johnny Hallyday, Eddy Mitchell et spécialement Vince Taylor, avant que la vague yéyé ne relègue au second plan les blousons noirs, à partir de 1963, le tournant a lieu le 22 juin 1963, lors de la « folle nuit de la Nation » : un concert gratuit organisé par Salut les Copains à Paris sur la Place de la Nation attire une immense foule, des incidents graves ont lieu, attribués (à tort ou à raison) à des bandes de blousons noirs. La scène yéyé prend définitivement ses distances avec ces derniers.

Les sociologues qui se penchaient alors sur les origines du problème de la délinquance juvénile évoquaient un conflit de génération ou une révolte contre l'ordre établi, avant d'avancer des facteurs économiques.La thèse la plus courante suggère que les jeunes de tous les pays ayant connu les privations de l'après-guerre se sont lancés à corps perdu dans la recherche de la liberté et le plaisir, voulant jouir immédiatement des biens que la société de consommations leur proposait: musique, moto ou mode. Mais pas assez riche pour pouvoir se les procurer et s'apercevant que la société n'était pas disposée à modifier ses habitudes, ni à ne leur faire aucune concession, ils se révoltèrent et leur enthousiasme se transforma en violence.

D'autres enquêtes au début des années soixante contestent cette thèse en soulignant l'importance de l'urbanisation dans le malaise des jeunes en mettant l'accent sur la concentration de grands ensembles immobiliers dans les villes véritables fabrique de blousons noirs.

"Les cités industrielles sont surtout pathogènes parce qu'elles favorisent les rassemblements de jeunes gens sur un territoire restreint " (109)

Effectivement, les bandes urbaines profilent surtout dans les quartiers abritant des grands immeubles collectifs type HLM ou des groupes d'habitations à bon marché souvent insalubre. Si les blocs HLM marquent un progrès certain par rapport au taudis, l'essentiel y manque trop souvent. La plus part du temps, il n'y a ni jardins, ni espace, ni équipement sportif sans parler de l'absence totale de distraction. Les enfants et les adolescents ont le sentiment d'être en cage et la rue les attire comme un refuge mauvais.

"On ne sait pas quoi faire, racontent des adolescents. Alors on se retrouve et on s'ennuie ensemble "

Parmi les autres facteurs on évoque souvent la carence d'autorité, mais c'est surtout dans la carence du milieu familial qu'il faut rechercher l'origine du drame des blousons noirs ; famille désagrégée, séparations ou divorces, alcoolisme du père.

Pour Henri Joubrel ; la dissociation familiale est la cause essentielle de la conduite asociale d'un nombre grandissant de jeune. Les statistiques montrent que 80 % des jeunes inadaptés sociaux dont on connaît suffisamment l'histoire pour en établir un dossier approfondi sortent d'un foyer dissocié. (111)

Au foyer, ils se sentent mal aimés, les gosses souhaitent la chaleur, ils trouvent le chaos

" Un soir en rentrant chez ma mère elle m'a virée, elle avait un jules " raconte Momo de la bande des Batignolles, après avoir traîné quelques jours dans les rues, le tribunal lui trouvera une famille d'accueil. (112)

" A quatorze ans, je suis parti travailler. Plâtrier. Pourquoi ? Parce que mon père boit et ma mère aussi ". écrit Jean dans Rallye Jeunesse (113)

Ce qui fait dire à un éducateur lyonnais :

" Ce qui déboussole souvent les jeunes, c'est l'impossibilité de prendre leur père pour modèle"

(114)

Si la société cherche les causes du mal dont souffre la jeunesse un autre facteur souvent négligé réside certainement dans le fait qu'ils sont victime de l'incompréhension des adultes. L'emblématique film " La Fureur de Vivre " évoquait déjà ces relations difficiles entre parents et enfant. A la question "mentez--vous à vos parents" posé par un journaliste qui enquête pour un hebdomadaire sur les problèmes de la jeunesse, des jeunes répondent :

" On ne ment pas, on ne parle pas ".

Puis lorsqu'il leur demande : " Que leur reprochez-vous ? ",

ils répondent: " Ils font vraiment une trop sale gueule à table ! " 58 (47)

Dans la même logique , une jeune fille, Raymonde écrit à Rallye Jeunesse

" Ce dont on souffre, c'est de l'ambiance familiale, du manque de vérité, de l'injustice de ce que nous appelons la "vague des croulants" " (116)Dans le conflit adultes jeunes, on assiste même à des faits incroyables comme histoire révélé par l'Humanité ou des jeunes émules des blousons noirs qui pétaradaient la nuit en scooter troublant le sommeil des citoyens de deux patelins ont été tondues par quelques habitants.

" La tête base, le crâne soigneusement tondu, suivant leur chef de fil qui de surcroît avait été dépouillé de son pantalon, plusieurs jeunes gens ont et promené dans les rues de Charly et de Vernaison près de Lyon sous l'œil marqué de la population… " (117)

109 « Les blousons noirs : une société primitive ? » - H.Michel (Directeur du centre de Vaucresson) – J.Selosse (Chargé de recherche au CNRS), In Sciences Avenir N°211, septembre 1964.

110 – « Les blousons noirs : une société primitive ? »

111 – « Mauvais garçons de bonnes familles » Henri Joubrel, Aubier, Editions Montaigne,1959

112 – « Square des Batignoles », Cinq colonnes à la une, 04/11/1960

113 - « Vous avez la parole », in Rallye Jeunesse N°11, février 1960.

114 – « Les garçons sauvage, le blouson noir, une provocateur mais aussi un mal aimé » Le Progrès de Lyon,09/12/1962

115 - "Mauvais garçons de bonnes familles" Henri Joubrel

116 – « Vous avez la parole », in Rallye Jeunesse N°11, février 1960

117 – « Tondeuse pour porteur de blousons », L’humanité, 21 juillet 1961 Si la bande est sociale dans sa structure, elle est par contre anti -sociale par son activité et par sa fonction. Si à l'origine elle ne semble pas se constituer dans un but délinquant, la bande est perçue sous cette forme par la police et la société. En réalité beaucoup de jeunes blousons noirs adoptaient uniquement un mode de comportement sans verser dans la délinquance mais s'exposaient de part ce fait à la réprobation sociale et à la répression. La plupart du temps les actes délictueux ne sont pas prémédités et sont commis dans l'inconscience la plus complète. On cherche surtout à réaliser un coup pour se valoriser sans vraiment se rendre compte de la gravité du délit.

" Ils ne se préoccupent pas exagérément des ennuis qu'ils ont eux avec la justice et ne s'inquiètent pas à l'idée d'avoir un casier judiciaire "(93)

Les Coeurs verts Edouard Luntz (cahiers du cinéma)

Les deux tiers des délits reprochés aux adolescents délinquants sont commis contre la propriété, dont les formes essentielles sont : le vol, les délits visant les deux roues et les actes de vandalisme.

Exemple type de l'activité d'une bande ; celle d'Arpajon dont la police a arrêté le mois de décembre 1959 une vingtaine de membres. Ces garçons âgés de 14 à 18 ans qui suivaient la plupart des cours professionnels dans la région parisienne, se réunissaient chaque jour sur le pont de l'Orge pour y préparer leurs "coups".

" Ils essayaient des blousons en plastique noir et se sauvaient sans les payer. Ils chipaient des disques, pour les écouter ou les revendre. Ils volaient des scooters et des voitures qu'ils abandonnaient hors d'usage. Ils faisaient main basse sur le contenu des autos en stationnement. Ils crevaient les pneus, allumaient des incendies ". (94)

Des adolescents par manque d'argent de poche pratiquent le vol à la tire et certain n'hésitent pas à faire les sacs des veilles dame. Le vol à l'étalage sert des fois pour l'alimentation des surboums. Le vol a parfois l'aspect d'un jeu, d'un défi lancé aux règles sociales.

Les objets volés sont souvent considérés comme des trophées et planqués dans des repaires. C'était le cas pour une bande de Nancy dont les exploits consistaient à voler les objets les plus hétéroclites au cours de cambriolage pour les tenir stockés dans une cave. Le chef de la bande âgé de 16 ans n'a pas hésité à tirer avec une carabine sur les inspecteurs de police venue les arrêter. Ce qui vaudra les assises à trois mineurs. Dans la même région à Charleville, un groupe de six mineurs de 14 et 15 ans connus sous le nom de " La bande des blousons verts " dirigé par un garçon de 20 ans commet 24 vols et cambriolages, le plus souvent la nuit, par effraction. (95)

Dans la région bordelaise chaque membre du gang des As avait son casier dans le garage abandonné qui leur servait de Q.G. on y trouvait les objets les plus hétéroclites, sous-vêtements féminins, couteaux, fer à repasser, boîtes de conserve, appareils photos, jouets, chapelets, rasoirs, statue religieuse etc. Leurs plus beaux trophées; une plaque minéralogique de car de Police Secours qu'ils conservaient jalousement dans leur repaire (96)

Certaines bandes étaient spécialisées dans le casse, lors d'un interrogatoire un jeune raconte avec cynisme ses exploits :

" En pleine nuit, quand nos parents dormaient, on se sauvait et on se retrouvait là... Là, on buvait pour se donner du courage, on s'habillait, on emportait la matraque, et on y allait. On s'habillait tous pareil, avec un masque, pour ne pas être reconnus. Ca commençait par les vitrines des petites veilles. On fait le coup en quelques secondes, à grands coups de matraques. On se donne même pas la peine de voler, ça ne nous intéresse pas... juste une bricole en guise de souvenir. Après le casse on se sauvait en vitesse par des ruelles d'où on n'avait rien pu entendre. On revenait fêter ça et on allait se coucher " (97)

  

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99) Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99)

Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

 

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

« LA SOCIETE NOUS AIME PAS, NOUS LES JEUNES ! »

Serge de la bande du Square des Batignolles (Cinq colonnes à la une 1960)

« Ces adolescents effondrés contre les murs, à la manière des cow-boys des westerns le long des cloisons des saloons, sont capables brusquement de lever le cran d'arrêt de leur énergie. Une poussée irrésistible les portes à imiter le Marlo Brando de l'Equipée Sauvage ou le James Dean de la Fureur de vivre"

Henri Joubrel, Jeunesse en danger, Fayard,1960

 

Les blousons noirs sont un phénomène essentiellement urbain. A Paris chaque porte, chaque quartier prolo possède sa bande. Un article de presse daté de l'été 1959 fait état de six bandes principales à Paris et de 70 autres cliques de moindre importance. (76) Selon la préfecture de police 10000 jeunes fréquentent des bandes dans la capitale. (77)

A l'époque la bande la plus importante de la capitale était celle du Talus capable de regrouper 250 à 300 jeunes le samedi soir. Ceux de la porte de St -Ouen se distinguent par la parfaite maîtrise des diverses langues des voyous. La bande du square des Batignolles et leur chef Pilule sont le sujet d'un reportage de l'émission télé Cinq colonnes à la une en 1960. Tout aussi médiatisée, la bande de la Bastille, forte d'une centaine de membres qui parlait un argot forcé. Une enquête est publiée sur eux l'été 1961 par Christian Magret dans le magazine des têtes couronnées Point de Vue. Le chanteur Moustique membre de ce groupe déclare quelques années plus tard dans un entretien:

" A la fin des années 50, on attaquait un car de flics, on cassait les vitres et on piquait le car pour une virée " (7

La bande du Sactos (Sacré Cœur) tournait aussi autour de la centaine et était protégée par leur curé. Elle était très crainte par les autres bandes. Johnny Hallyday qui faisait partie de la bande du square de la Trinité raconte :

«On jouait les durs. On se battait, mais nous fermions notre gueule lorsque la bande du Sacré-Cœur descendait" (79)

La plupart des bandes se singularisaient en arborant le même signe distinctif, qui allait de la manière de se coiffer, aux différents accessoires ; médailles, voir une tête de mort ou un minuscule couteau retenu au cou par une chaîne, bagues, bracelets ou ceinturons incrustés de pièces de monnaie. Cette singularité se retrouve sur leurs engins à deux roues; mobylettes ou scooters : fanions à tête de mort, hélices en plastique de la même couleur gagnées à la fête foraine. La même décalcomanie collée sur le réservoir ou le garde boue ; photos de Tarzan ou de James Dean, vamp, tête d'indien, trèfle à 4 feuilles. L'accessoire peut donner son nom à la bande, ainsi la bande du Damier d'un port breton arborait un damier sur leurs véhicules.

En 1960, 53 % des jeunes qui fréquentaient les bandes sortaient de familles ouvrières, les fils d'employée représentaient 12%.

A noter que 18 % des effectifs des bandes seraient originaires des milieux sociaux supérieurs.

" La majorité de ces jeunes étaient issue des classes sociales défavorisées bien que la bourgeoisie eut ses blousons dorés. Les bandes constituent une configuration culturelle originale, articulée sur une culture de classe. La culture ouvrière en est le soubassement " (80)

Les adolescents de 15 à 17 ans en constituent le noyau le plus important (53, les plus jeunes de 13 à 14 ans représentent 14,8% des membres et ceux de 18 à 20 ans 18,1 % (81) Les blousons noirs des années 1959-1961 appartiennent à la génération des enfants de la guerre, ceux nées pendant la seconde guerre mondiale entre 1939 et 1945 et dans l'immédiate après guerre.

 

Les bandes tournent généralement autour de trois noyaux. Le noyau central composé de ceux qui étaient le plus en vue, quatre à cinq personnes souvent confrontées à la délinquance. Puis vient la bande proprement dite formée en moyenne d'une quinzaine à une vingtaine de membres qui cherchaient surtout à se faire remarquer. Le troisième noyau qui pouvait être plus important jusqu'à une centaine de jeunes était composé des sympathisants et des postulants qui formaient le halo de la bande présent lors des grandes occasions comme une bagarre entre bandes rivales. La bande forme un milieu homogène, l'embryon en est la "cour " où les enfants d'un même immeuble vivent et grandissent ensemble. Vers l'âge de 12 ans les enfants de plusieurs cours se groupent dans des lieux de rencontre plus vaste : places ou squares où ils se forment en bande. Dans la bande, les adolescents se retrouvent et ne s'expriment qu'en symbiose avec les autres.

Le dynamisme du groupe est contenu dans ses motivations qui portent le jeune à avoir en face de lui des interlocuteurs qui le comprennent, qui ont les même besoins et les mêmes soucis que lui et ne par conséquent être des adultes qu'ils haïssent.

" Les vieux ont s 'en fout, ils peuvent tous crever” répond spontanément un jeune blouson noir au juge d'instruction qui lui parlait de ses parents (82).

Pour son reportage dans l'Express, Jean Cau demande à Jojo de la bande de la Porte de Vanves. " Pourquoi "les vieux" à ton avis ne vous comprennent pas ? " réponse de Jojo : " Parce que qu'on voit la vie autrement ! " " Qu'est ce que tu veux dire ? " lui demande alors l'écrivain. Le blond répond à sa place : " Ils voudraient qu'on porte des gilets, qu'on ait des pantalons comme ça, qu'on soit comme eux ! " (83)

Ensemble, ils reconnaissent être différents des autres, mais cette différence, paradoxalement se manifeste par le maximum de conformité avec ceux du groupe. C'est pour cela que le vêtement, la coupe de cheveux, le langage ont une telle importance, ils manifestent une singularité collective. Mais si la panoplie marque la rupture avec le monde adulte, elle ne devait pas être usurpée. Il faut être reconnu par ses pairs, il y a des modèles, l'orgueil, l'honneur et l'exploit ont une grande place dans la vie des bandes. L'intégration dans une bande n'est pas une chose facile. La bande est une société tellement fermée qu'y pénétrer est incontestablement une victoire. Elle passe par deux étapes, celle de la reconnaissance puis celle de l'acceptation. Pour être accepté, il y a des rites d'admissions. Le postulant doit faire ses preuves en réalisant divers exploits qui pouvaient aller du combat au cran d'arrêt à la course de mobylettes dans les sens uniques ou sur les " fortifs " (Certains tronçons des fortifications de 1870 subsistaient encore dans la capitale à la fin des années 50 (84). Parmi les autres exploits couramment pratiqués ; se battre avec le chef ou piquer une nana dans une bande ennemie. Ces pratiques sont souvent associées avec le rituel du " frère de sang " Le chef du gang entaille avec son couteau l'avant bras du postulant, puis fait la même estafilade en forme de croix sur celui du dernier rentré dans le groupe. Il maintient leur deux bras ensemble, unis par le mélange de leur sang, les deux "frères" jurent que jamais ils ne trahiront leurs camarades. Une autre caractéristique de la bande est le vif sentiment de propriété vis à vis de son territoire. Elle a ses lieux de réunion, ses cafés et ses cinémas et n'en change pas et ne tolère pas qu'une autre bande vienne empiéter sa zone, sinon c'est la guerre. Le square, mini espace de verdure apparaît l'endroit idéal pour leurs rassemblements. Là, les garçons discutent ensemble, se racontent des histoires de filles ou de taules souvent exagérées. Ils s'échangent des idées, blaguent, s'amusent, se chamaillent entre eux tout en écoutant de la musique sur un transistor. Dans ce lieu, où ils traînent souvent tard le soir les adolescents éprouvent un sentiment de liberté.La fête foraine est un autre coin qui les attire, et ils aiment se regrouper autour des auto-tamponneuses. Il y règne une certaine ambiance, adossés à la balustrade, ils prennent plaisir à regarder tourner les voitures en écoutant les derniers disques à la mode ou draguer les filles. L'hiver on se met au chaud dans les salles de jeux avec une prédilection pour le flipper. Au Café, ils ne consomment pratiquement pas d'alcool, préférant le diabolo ou le café crème. Paris, connaît l'hiver 1959 la grande vogue du patin à glace. Les patinoires de Saint Didier ou de la " fédé " de Boulogne sont prises d'assaut par des hordes de gamins.

" La fédérale c'est la roue tournante de tous les blousons noirs, on retrouve les copains de tous les quartiers. Il y a des filles, ce n’est pas cher et on s'amuse bien " raconte Pilule chef de la bande des Batignolles (85). Quant au bal, ils y vont très rarement la plupart de ces garçons ne savent pas danser, mais sur place ils aiment bien provoquer des bagarres.

" Le soir d'une fête patronale une quarantaine de jeunes venus de Rouen à scooter, à cyclomoteur ou en taxi, avaient plusieurs fois tenté de pénétrer dans la salle de bal en refusant de payer. L'expulsion par les gendarmes de deux ivrognes leur fournit le prétexte recherché pour passer aux actes de violence. Toute la bande se rua alors sur les représentants de l'ordre et l'un des gendarmes fut roué de coups. Son collègue tira quelques coups en l'air. Ce geste décontenança un temps les agresseurs mais les gendarmes partis, les jeunes gens pénétrèrent en force dans la salle où il brutalisèrent plusieurs danseurs et plusieurs femmes "(86)

Les bandes importantes comportent parfois un tiers de filles. On y trouve souvent des filles garçons qui rêvent d'être des garçons et se conduisent comme tels. Elles revendiquent leur égalité dans les comportements antisociaux et le manifestent notamment par des attitudes de bravades vis à vis de la police lorsque celle-ci intervient. Le journal le Progrès de Lyon raconte le comportement de deux filles membres d'une bande du quartier de Perrache après leur arrestation :

"On reste confondu lorsque l'on sait que ce sont les deux filles qui tinrent tête avec le plus d'aplomb au commissaire et firent preuve d'une inconcevable impolitesse. L'une se contenta de dire : "Je me fous de la police, je me fous de la famille" L'autre, encore plus effronté, n'alla-t-elle pas jusqu'à déclarer : " Parlez moins fort. Vous me faites mal aux oreilles…" (87)Mais la majorité des adolescentes qui fréquentent les bandes peuvent être classées dans la catégorie des "filles-objets" guère respectée qui servent à l'initiation sexuelle des garçons. Elles vont d'un garçon à l'autre, et prennent une sorte de valeur marchande en se faisant échanger pour trois fois rien! Il y aussi les filles attitrées que possèdent les principaux membres de la bande, qui souvent par prudence sont rarement vues par les autres gars. Les filles participent rarement aux délits, mais en sont les complices indirectes en bénéficiant souvent en forme de cadeaux des produits dérobés. Elles aiment se faire conduire dans des véhicules volés, ce qui donne un certain prestige à l'auteur de l'acte délictueux. La délinquance est souvent un moyen de se poser en homme devant la femme pour obtenir ses faveurs. Si quelques séries B américaines de la fin des années cinquante ont fait des gangs de filles l'un de leurs thèmes favoris. L'existence de quelques bandes féminines en France a été confirmée par certains enquêteurs. Lorsque le journal La Montagne évoque une agression commise par une bande de jeunes filles à Caen, on emploie symboliquement le terme de "jupons noirs" : "Les jupons noirs de Caen rouent de coup un Nord-Africain" (8 On note surtout une délinquance féminine opérée en petit groupe dans les grands magasins. Une fille achète un produit pour occuper la vendeuse, une autre fait le guet, tandis que la troisième vole des vêtements ou des aliments. Comme dans l'histoire du film de Marcel Carné " Terrain Vague " on signale des gangs de garçons dirigés par une fille. Exemple, le gang des As une bande délinquante de la région bordelaise qui avait à sa tête Berthe une gamine de 16 ans. (89)

Terrain Vague

Le rapport au travail du blouson noir est complexe. Le gars qui à l'habitude de vivre en bande n'a pas envie de la quitter pour aller bosser, tandis que celui qui travaille de voir ses copains traîner toute la journée lui donne des mauvaises idées et il s'arrête de travailler. Le marché de l'emploi de l'époque le permettant, on travaille selon l'envie ou la nécessité.

" Si le gars travaille, un moment, pendant une semaine ou un ou deux mois, c'est qu'il a besoin d'argent pour s'habiller, pour manger, pour s'acheter une mobylette. Ou bien c'est qu'il s'est produit un renversement moral: son instinct est devenu faible et sa volonté lui a permis de travailler pendant ce temps là " (90)

" Je travaille quand j'ai besoin de fric. S'il me faut une paire de " groles ", je fais la plonge. Si c'est une nécessité plus grave, je me fais embaucher un mois ou deux dans mon métier" . Raconte Guy 18 ans (91)

Les contrats d'apprentissages sont la plupart du temps des contrats pour la forme. Les patrons en profitent pour mal payer les jeunes, mais ils les font travailler comme des ouvriers adultes. En plus, les jeunes apprentis supportent mal les ordres des chefs d'équipes, de ce fait, ils changent régulièrement de métier. Le plus souvent les jeunes des bandes qui travaillent exercent des métiers sans grande qualification comme: télégraphiste, plombier, graisseur. Des métiers où la main d'œuvre est variable qui leur permet de changer de patron, de lieu de travail à leur guise. Lorsqu'on demande à Moustique le benjamin de la bande de la Bastille qui ambitionne de trouver un boulot " pépère " quel genre de travail il aimerait faire, il répond: " Ben : aide routier, livreur en triporteur ou alors être le fils de taulier, avoir une carte de figurant de cinéma ".(92)

 

76 – Philippe Macaigne "Quelques réflexions sur la présentation de la presse écrite des "blousons noirs", in Annales de Vaucresson, N° 2,1964

77 - C.Freinet, « La formation de l’enfance et de la jeunesse », Edition l’école moderne, 1960

78 - Interview Moustique par Christian Victor in Juxe-Box Magazine N° 86, novembre 1994

79 - Interview Johnny Hallyday par Jacques Barsamian in Juke Box Magazine N° 42, novembre 1990

80 - Jean Charles Lagrée in "Les jeunes chantent leurs cultures", page 19,L’Harmattan , 1982

81 - Rapport annuel de l’Education surveillé pour 1960 in "Les bandes d’adolescents","Les classes d'age" page 3 Philippe Robert, Pierre Lascoumes Les éditions ouvrières,Paris 1974

82 - "Les vieux ? qu'ils crèvent ! « Le mal de la jeunesse » ,in Faim & Soif N°33, 7/02/1960

83 - Jean Cau, Les gosses révoltés, l'Express 30 juillet 1959

84 - Long Chris "Johnny", page 17,J'ai Lu N°2380,

85 - "Square des Batignoles" Reportage de Pierre Dumayet, Cinq colonnes à la une,4/11/1960

86 - « Quand la jeunesse faisait peur », Laurent Mucchielli, chercheur au CNRS

87 - "Des blousons noirs sont surpris dans leur repaire par les policier" in Le Progrès de Lyon, 22 mai 1962

88 - La Montagne, 18 juin 1960, Claire Bacher 3Le phénomème bmousons noirs vu par la presse Maitrise faculté de Clermont Ferrant 2000

89 -Philippe Parrot, Monique Gueneau "Le gang des As" in "Les gangs d’adolescents",PUF,1959

90 - in "Cri d'appel d'un blouson noir", page 47, Fayard, 1962

91 - In “tribune libre des jeunes” Cinémonde 16/10/62

92 - in "Les Blousons

 

Blousons noirs. Soixante ans après, l’expression a gardé toute sa force évocatrice, porteuse d’une mythologie cuir mêlant violence et rock’n’roll naissant sur fond de désœuvrement et de misère sociale (ça ne vous rappelle rien ?). Le festival Filmer la musique, que Poptronics suit quotidiennement, y consacre une journée entière avec deux films, une séance de documents d’actualité d’époque et un concert de Magnetix en clôture au Point Ephémère.

1955, « Graine de violence » (« Blackboard Jungle ») sort au cinéma. C’est l’émeute : la jeunesse française découvre en même temps les déhanchements de Presley et le « Rock Around The Clock » de Bill Haley. Les choses ne seront plus tout à fait pareilles : le rock’n’roll vient d’entrer dans la culture populaire hexagonale. Et avec lui, ceux qu’on appelle encore les « tricheurs », d’après le titre du film de Marcel Carné qui sort en 1958, ces jeunes banlieusards des cités qui sortent de terre. Il y a déjà eu quelques gros incidents : à l’été 1955, un concert de Louis Armstrong déclenche une bataille de trois jours dans les rues de Paris, en octobre 1958, le concert de Bill Haley à l’Olympia donne lieu à des débordements : des fauteuils sont détruits par centaines.

  

Mais c’est à l’été 1959 que la France découvre, tétanisée, les blousons noirs. Le 24 juillet, vingt-cinq jeunes de la Porte de Vanves déboulent dans le XVe arrondissement pour affronter la bande du square Saint-Lambert, vêtus de blousons de cuirs, de jeans, et armés de chaînes de vélo. Le lendemain, on se bagarre à Bandol pour une histoire de filles. Quelques jours plus tard, un policier est blessé à Cannes lors d’affrontements avec une bande de Courbevoie. L’affaire fait la Une (« Un agent de police a été sauvagement poignardé par une horde de tricheurs, de blousons noirs »). Les incidents se multiplient tellement (à la sortie de « Jailhouse Rock » en 1960, le cinéma Le Mac Mahon est littéralement pris d’assaut) que le sinistre Maurice Papon, préfet de police de Paris depuis 1958, songe très sérieusement à interdire le rock’n’roll pour préserver la « tranquillité publique ». Cette peur diffuse de la jeunesse, on la retrouve dans les reportages de l’ORTF,

 

Revenir en haut Aller en basDans quel contexte apparaissent les blousons noirs ?

C’est de la délinquance sur fond de rock’n’roll, de guerre d’Algérie et surtout de naissance des cités. A l’époque, face aux barres de Nanterre, La Défense est un immense terrain vague sur lequel seul le Cnit est construit. A peine sortie de terre, cette urbanisation est déjà porteuse de problèmes et provoque désœuvrement, ennui, marginalisation. Il ne fallait pas être visionnaire pour voir que ça allait être le bordel : l’environnement, c’est déjà celui de « Ma 6-t va crack-er ». Cette jeunesse ouvrière qui traîne en bas de ces grandes barres HLM nickel s’emmerde et se radicalise. Les blousons noirs terrorisent les gens, ils niquent toutes les nanas, qui toutes veulent être niquées par eux ! Ils n’ont pas de conscience politique, pas vraiment de conscience sociale non plus, ils sont dans l’énergie brute : ils foutent le bordel et c’est tout.

Quand le mouvement devient-il massif ?

Quand Hallyday débarque, en 1961. C’est un choc. Jusqu’alors, le business de la musique est aux mains de vieux qui se projettent sur les envies des jeunes et suivent les modes. On a affaire à des orchestres de bal qui jouent du twist, quelques mois plus tard ils font du cha-cha ou du calypso. Hallyday, lui, fait de la musique pour les jeunes sans une once de cynisme. Et ça, les kids, ça leur fait péter les plombs. Quand Johnny ou Vince Taylor jouent à l’Olympia au début des années 60, ils cassent tout, ça fait la Une des journaux, avec des slogans choc, ça fait flipper tout le monde car cette expression de la violence des jeunes en groupe est assez nouvelle. Les blousons noirs succèdent en quelque sorte aux apaches du début du siècle, qui eux étaient vraiment dans le banditisme. Là, ce sont des branleurs. C’est assez inédit.

C’est une esthétique aussi...

Oui, les blousons en cuir, les jeans, on est complètement dans le fantasme du motard, de « L’Equipée sauvage ». Brando, avant James Dean, devient une véritable icône de cette jeunesse. Il y a un côté désuet à les revoir aujourd’hui, un mélange de pathétique et de sublime. Le phénomène est assez européen, très présent en Suisse, en Allemagne, mais en France, c’est quelque chose de dur, le cuir, les chaînes, il y a une volonté d’effrayer le bourgeois, de faire peur, un vrai désir de choquer et de provoquer. Aux Etats-Unis, on ne trouve pas tous ces atours, tout cet apparat.

Les blousons noirs disparaissent peu à peu au cours des années 60. C’est la fin du rock’n’roll dans les cités ?

Difficile de dater la fin du mouvement, beaucoup rentrent dans le rang assez vite (selon quelques rares études, plus de la moitié des blousons noirs ont entre 14 et 17 ans, huit sur dix ont moins de vingt ans, ndlr), une petite frange tombe dans la vraie marginalité. Mais le rock ne disparaît pas pour autant du paysage banlieusard. Le rock’n’roll n’a quitté les cités qu’avec l’arrivée du rap. Jusqu’au début des année 80, tout le monde y écoute du rockabilly et du rock’n’roll, qu’on soit blanc, black ou arabe. Gene Vincent est une star des cités. D’ailleurs, ceux qui ont fondé les premiers labels de rap étaient tous d’anciens fans de rockabilly. La naissance des blousons noirs La bande de « Titine » au pied des HLM du Pré-Saint-Gervais. 'agression du jeune Yuriy, en janvier dans le X Ve arrondissement de Paris, a mis en lumière les affrontements entre bandes. Mais à la fin des années 1950 déjà les héritiers des Apaches de la Belle Epoque n’avaient peur de rien ni de personne. Ils aimaient la castagne, les Mobylette et le rock’n’roll. Immersion chez ces petits voyous du Pré-Saint-Gervais, avec le photographe André Lefebvre. La vague est partie des Etats-Unis. Leurs références sont James Dean et sa « Fureur de vivre », Brando dans « L’équipée sauvage ». Partout, ce sont les mêmes jeunes en proie au même mal du siècle. En Angleterre , on les appelle les « Teddy boys », en Allemagne les « Halbstarken », en Suède, les « shunna folke », en France ce sont « les blousons noirs ». L’expression est lancée par le journal « France-Soir », à l’été 1959, après un affrontement entre bandes, square Saint-Lambert, dans le XVe arrondissement de Paris. Avec leurs manteaux de cuir, leurs cheveux mi-longs gominés, leurs chaînes de vélo et leurs poings américains, ils se rassemblent au pied des tours ou des pavillons aux façades décrépies, dans les quartiers populaires des villes ou de leur périphérie. La plupart du temps, les blousons noirs appartiennent à la classe ouvrière, vivent de petits boulots et grandissent dans des familles éclatées. Ils sont les laissés-pour-compte des Trente Glorieuses marquées par l’essor économique et l’émergence de la classe moyenne. Dans le groupe du Pré-Saint-Gervais qu’ont suivi Jean Maquet et André Lefebvre, les journaliste et photographe de Match, la moyenne d’âge est de 16 ans. « Ces jeunes gens sont tout au plus égarés, ils ne sont pas vicieux. Ils vivent en bandes, certes, mais ce mot de bande est trompeur. On pense aux bandes de gangsters, écrit Jean Maquet [...]. Les membres des bandes de blousons noirs, dans l’immense majorité des cas, ne sont que des copains. Il faut insister sur ce point. Il serait on ne peut plus néfaste, et pour tout le monde, que le public se fasse du blouson noir une idée trop noire [...]. Le problème des blousons noirs est grave : il n’est pas encore tragique. » Des copains qui inventent leur propre culture, de nouveaux codes.

Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes @ Sur leurs postes de radio, ils écoutent le rock’n’roll d’Elvis Presley ou de Vince Taylor. Très loin des yéyés. « Ils ont besoin de se sentir virils », écrivait le journaliste de Match. « Cela donne la baston, c’est-à-dire le règlement de comptes à mains nues entre hommes, et, de temps en temps, la “frite”, c’est-à-dire la bagarre générale [...]. Bref, la violence. » Une violence gratuite, pour passer le temps, par exubérance juvénile, par désir de se montrer brave. On se bat pour s’imposer, prendre le pouvoir dans le quartier ou juste pour la gloire, on se tape des virées dans des voitures volées… Ils commettent des larcins, pillent ou cassent plus par défi que par besoin ou conviction. Et, s’ils brandissent leur haine des « flics » et de l’ordre bourgeois, ils ne défendent aucune cause. Leur conscience politique ne ressemble en rien à celle des étudiants de Mai 1968 qui crieront leur révolte quelques années plus tard. Malgré leur rejet de l’autorité, les bandes sont hiérarchisées autour du chef et de ses lieutenants, qui ont tous un surnom. Pour en être, il faut respecter certains rituels, être initié, savoir se montrer téméraire, commettre un vol ou se mesurer à un rival. La presse, qui s’est emparée du phénomène, en fait un mythe. Un congrès sur la délinquance juvénile est même organisé en Italie. Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes. Parmi eux, 45 000 ont moins de 18 ans. Comme les loubards ou les jeunes des cités après eux, ils veulent s’affirmer, interroger la société, la provoquer, mettre à l’épreuve sa capacité à les intégrer. En marge, cette jeunesse défavorisée est gangrenée par le désœuvrement. « Sur ce point, ils sont unanimes. Ils s’ennuient, écrivait Jean Maquet. Ils sont incapables de rester seuls. La bande, cette bande fluctuante, c’est ce qui les délivre de leur solitude, leur donne l’illusion d’une fraternité et sans doute, pour beaucoup d’entre eux, d’une famille. Ils ne lui en demandent pas plus. » 69 VENISSIEUX Les MJC 1959-1981 De l'été des blousons noirs à l'été des Minguettes Broché – 3 avril 2008 Les Maisons des jeunes et de la culture (MJC) font partie de ces institutions méconnues bien que souvent évoquées. Parfois confondues avec les Maisons de la culture d'André Malraux, parfois assimilées à de simples maisons de jeunes, elles sont victimes de l'ampleur de leur objectif : lier jeunesse et culture dans une perspective d'éducation populaire. Ce livre retrace leur histoire à leur apogée, entre 1959, lorsque la médiatisation du phénomène blousons noirs favorise une mobilisation en leur faveur, et 1981, quand l'apparition du " mal des banlieues " signalait un changement d'époque : l'insertion sociale des jeunes devenait une priorité tandis que le lien entre jeunesse, loisirs et action culturelle achevait de se dissoudre dans la crise du socio-culturel. Entre ces deux dates, le millier de MJC que comptait alors le territoire a connu une histoire aussi riche que mouvementée. La diversité des activités abritées dans leurs murs n'a d'ailleurs pu que contribuer à rendre les MJC difficilement saisissables : tour à tour foyers de jeunes et maisons pour tous, proposant expérimentations théâtrales et ateliers de bricolage, espaces de débats et sociabilité, elles furent aussi des pépinières pour la formation de militants culturels et politiques locaux. Lieux singuliers qui ont pu être présentés, parfois simultanément, comme des repaires de gauchistes, des centres de propagande communiste et des terreaux de la deuxième gauche, les MJC permettent de saisir la complexité de la vie associative, dans sa richesse mais aussi sa difficulté. Voilà un très beau livre de synthèse sur un sujet qui ne peut manquer d’intéresser les lecteurs de cette revue. Même si les MJC (Maisons des jeunes et de la culture) n’avaient pas pour finalité de contribuer à la lutte contre la délinquance, elles ont été parfois perçues par les municipalités comme un des outils efficaces de prévention, en particulier à l’époque des blousons noirs. Le sous-titre adopté par l’ouvrage rappelle d’ailleurs cet impact possible ou souhaité sur la prévention. Mais Laurent Besse a bien d’autres ambitions ici, et il analyse les MJC à l’aune de l’éducation populaire, et de ses grandes ambitions au lendemain de la Libération. Il les suit donc depuis la République des jeunes, dont l’idée est née au sein du gouvernement de la France libre à Alger (d’après leur fondateur André Philip), jusqu’à l’arrivée de la gauche au pouvoir. En fait, il commence surtout avec leur très forte expansion sous le régime gaulliste avec la nomination de Maurice Herzog, fin 1958, comme haut-commissaire à la Jeunesse et aux Sports. La préface d’Antoine Prost souligne d’ailleurs le paradoxe des MJC : ce sont des institutions de gauche surtout présentes dans les villes de droite et du centre, et Laurent Besse montre que les MJC bénéficient avec Herzog d’un appui essentiel. En 1965, lors de l’anniversaire de leurs vingt ans, la fédération des MJC compte trois fois plus de maisons qu’en 1959. Deux autres paradoxes, soulignés par Antoine Prost, caractérisent les MJC. Elles sont laïques, mais mal vues de la Ligue de l’enseignement. Elles sont destinées aux jeunes, mais accueillent bien d’autres classes d’âge.

2Issu d’une thèse soutenue à Paris-I en 2004, ce livre repose sur une abondante documentation, permettant d’analyser les réactions du tissu local comme les enjeux nationaux, la sociologie des directeurs autant que la philosophie des fondateurs, les pratiques de loisirs autant que les ambitions culturelles. Si les archives de la fédération FFMJC (Fédération française des maisons de jeunes et de la culture), et de la fédération concurrente UNIREG (Union des fédérations régionales de MJC) à partir de 1969, ont été essentielles, elles ont été heureusement complétées par celles des douze principales fédérations régionales, et celles des MJC de quelques grandes villes (Châtellerault, Grenoble, Orléans) ainsi que de fonds privés de militants. L’ouvrage est donc parfaitement étayé, foisonnant de précisions qui en rendent la lecture vivante, et qui n’effacent jamais le souci d’une réflexion synthétique.

3Le livre est bâti sur une chronologie fine, qui distingue trois périodes au cours de ces deux décennies, qui ont vu la multiplication des MJC et leur ouverture à un public élargi. Les 14-21 ans y sont majoritaires dans la décennie 1960 (cf. la première partie « Des maisons pour les jeunes - 1959-1965 »), recrutés parmi les « inorganisés », qui n’appartiennent à aucun mouvement, et dont on souhaite qu’ils viennent aussi bien du monde des ouvriers (les travailleurs manuels), que des étudiants (les lycéens). Le projet des initiateurs des MJC (et l’auteur insiste sur le portrait d’André Philip et de sa philosophie de laïcité ouverte) est d’ouvrir une maison de loisirs culturels et éducatifs pour cette classe d’âge, tous milieux sociaux confondus. Le pari est tenu, en particulier autour des activités de ping-pong et de judo.

4La deuxième partie (« Maisons contestées ? Maisons de la contestation ? 1966-1969 ») insiste sur le choc qu’a été pour la fédération des MJC le départ de Maurice Herzog et son remplacement par François Misoffe, devenu ministre de la Jeunesse et des Sports, hostile aux animateurs et décidé à étouffer ces maisons de la contestation et à les remplacer par « mille clubs » beaucoup plus légers. La fédération est déstabilisée et même si le projet ministériel de suppression de la FFMJC échoue, André Philip démissionne. La FFMJC a fait figure d’administration parallèle et cela ne pouvait pas laisser le pouvoir gaulliste indifférent. C’est le moment aussi où les MJC s’ouvrent aux débats et, sans être le fer de lance de la contestation en 1968, s’en font la caisse de résonance.

5L’interrogation sur « Des maisons pour tous (1970-1971) » qui structure la dernière partie, repose sur le fait que les MJC accueillent alors un public nouveau, de femmes et d’enfants, relativement inconnu jusqu’ici, que l’animateur militant laisse la place peu à peu aux vacataires compétents. Elles deviennent des maisons de loisirs pour tous, et des lieux d’une autre culture, avec multiplication de débats sur les marges et les luttes de tous les peuples. Elles accueillent des chanteurs compositeurs débutants et créent des spectacles appelés à circuler. À la fin des années 1970, la mise en cause du socioculturel est l’enjeu de débats passionnés, et le développement de la crise amorce la réflexion sur l’insertion économique des jeunes autant que sur leur développement culturel. Mais les MJC ne sont pas les seules sur ce terrain…

6Tout au long de l’ouvrage est tenu le fil de la réflexion sur l’éducation populaire, sur ses objectifs, ses contenus, depuis l’ambition des origines, jusqu’aux crises mettant en cause la survie même des MJC, aux prises avec les politiques locales et nationales. Comment développer l’éducation populaire ? Comment intégrer ceux qui refusent la participation régulière aux ateliers, préférant les rencontres informelles du foyer autour du baby-foot ? Comment faire coexister les « intellectuels » avec les autres ? Comment, sans exclure, désamorcer les agressivités, les déprédations ? Le livre aborde l’émergence du métier d’éducateur, qui s’est faite précisément au sein des MJC, dans un milieu qui a longtemps préféré le terme de « directeur » (même en pleine affirmation de la non-directivité des années post 68) à celui d’animateur. Comment les recruter, comment les former ? Il insiste sur le fait que les MJC ont été des équipements discrets, à la différence des maisons de la culture, qui, par comparaison, s’affirmaient dans le paysage urbain comme temples de la culture.

7L’analyse culturelle est étroitement imbriquée dans l’analyse des politiques nationales de la jeunesse, mais aussi des politiques locales. La position originale des MJC qui sont des associations 1901 cogérées avec les municipalités, si elle fournit une initiation à la vie démocratique, est aussi source de conflits avec les municipalités. La place du parti communiste, souvent surestimée, fait des MJC des lieux inquiétants pour les élus de la droite, bien que certains, dans bien des villes, leur soient restés fidèles, sensibles à la qualité de leur travail. La comparaison avec les centres sociaux, beaucoup plus marqués par les militants JOC, en fait ressortir la spécificité essentielle dans une jolie formule. Pour Laurent Besse, le centre social, c’est « l’espace des poussettes », alors que la MJC est « l’espace des mobylettes ».

8La conclusion de Laurent Besse est sévère. Pour lui, l’action des MJC se solde par un relatif échec, dans la mesure où elles n’ont pas été capables de s’adresser en masse aux jeunes. Certes, elles ont été les fruits d’une très grande ambition qui aurait pu faire d’elles, sous la IVe République, ce que les maisons d’école avaient été à la IIIe, et des éducateurs populaires, les nouveaux instituteurs de la République. Certes, elles ont bénéficié de la crise des mouvements d’action catholique. Néanmoins, leur projet de devenir le banc d’essai de la citoyenneté, d’être écoles de la démocratie, n’a pas abouti. L’auteur souligne cependant l’offre qu’elles ont apportée à nombre de petites villes et de villes de banlieue, qui seraient restées des déserts culturels sans elles. Mais leur humanisme polyvalent, qui voulait que l’homme complet soit initié à toutes les disciplines, a cédé devant la spécialisation de la vie associative. En outre à la fin des années 1970, l’heure n’était plus à l’animation, mais à l’insertion professionnelle des jeunes. Et Laurent Besse de conclure sur les difficultés actuelles des MJC, à replacer dans « le contexte de déclin de la ferveur éducative, peut-être de l’utopie éducative ».

Haut de page

Pour citer cet article

Référence papier

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière », 12 | 2010, 256-259.

Référence électronique

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière » [En ligne], 12 | 2010, mis en ligne le 21 juin 2012, consulté le 27 juin 2021. URL : journals.openedition.org/rhei/3212 ; DOI : doi.org/10.4000/rhei.3212

Haut de page

Auteur

Dominique Dessertine

Articles du même auteur

Histoire de l’éducation populaire (1815-1945). Perspectives françaises et internationales [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 22 | 2020

Ces êtres intéressants et infortunés : les enfants trouvés des Basses-Alpes au XIXe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 20 | 2018

Droits des enfants au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 19 | 2017

L’œuvre de secours aux enfants et les populations juives au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 18 | 2016

Jean-Pierre Méric, Les pionniers de Saint-Sauveur : la colonie agricole du Médoc pour les enfants trouvés (1844-1869) [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 16 | 2014

(Lecture de) Des enfants venus de loin. Histoire de l’adoption internationale en France [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 15 | 2013

Tous les textes...

Les blousons noirs sont une sous-culture juvénile apparue en France dans les années 1950 et qui a connu son apogée entre 1958 et 1961. Issue de l'influence américaine, connotée à un code vestimentaire particulier et au rock'n roll, elle a été la matrice originelle du mouvement yéyé et de quasiment toutes les modes adolescentes ultérieures. Des sous-cultures similaires ont fleuri au même moment dans d'autres pays d'Europe.

La culture « blouson noir » s'est cristallisée autour d'importations américaines qui ont été autant de chocs culturels :

Le film L'Équipée sauvage (The Wild One), sorti en 1953 aux États-Unis mais popularisé courant 1955 en Europe, où le personnage interprété par Marlon Brando révèle d'un coup une façon d'être qui fait époque : cuir noir, moto, machisme, volonté de choquer, esprit de gang, violence à la limite de la criminalité.

Un autre film, La Fureur de vivre (Rebel Without a Cause) arrive en 1956 en France et fait de James Dean une icône définitive. Il introduit l'idée importante que le comportement des (futurs) blousons noirs n'est pas seulement un choix délibéré mais procède d'une fatalité générationnelle et de l'incompréhension des adultes.

L'arrivée au même moment du rock'n roll (Bill Haley et Elvis Presley en premier lieu, puis Gene Vincent, Eddie Cochran etc.) ajoute le son à l'image. Mais c'est une chanteuse française a priori non associée au rock'n roll qui apporte en 1956 une énorme visibilité médiatique au phénomène en formation, Édith Piaf, avec la chanson L'Homme à la moto, indirectement inspirée par L'Équipée sauvage.C'est durant l'été 1959 que l'appellation « blousons noirs » apparaît pour la première fois dans la presse, avec un article de France-Soir du 27 juillet 1959 relatant un affrontement entre bandes survenu au Square Saint-Lambert, dans le XVe arrondissement de Paris[1]. Cette désignation s'impose soudain comme synonyme de « jeunes voyous ». Les journaux se mettent alors à surenchérir en évoquant des bandes caractérisées par leur taille importante (il est question de groupes comptant jusqu'à une centaine de jeunes) et par leur violence. Les « blousons noirs » sont décrits comme des asociaux qui se battent à coups de chaînes de vélo (ou de moto), de coups de poing américains voire de couteaux à cran d'arrêt, qui cherchent la bagarre pour défendre leurs territoires urbains, particulièrement autour des portes de Paris, ou en faisant des descentes dans des bals ou des fêtes.Peu après, les journalistes forgèrent le terme « blousons dorés » pour désigner les jeunes fils de la bourgeoisie qui se faisaient remarquer dans les faits divers, par opposition aux « blousons noirs » qui étaient plutôt issus de milieux populaires.

Cette campagne de presse, qui tourne à la psychose collective, aura pour principal effet de mettre en vogue le genre blouson noir. Autour de 1960, dans tout le pays et dans tous les milieux sociaux, les jeunes gens à la mode aiment à s'habiller de cuir (mais le véritable Perfecto est encore rarissime), portent de grosses chemises à carreaux, se coiffent en arrière avec au sommet du front une large boucle asymétrique souvent brillantinée (la célèbre « banane »). À défaut d'une véritable moto, luxe accessible seulement aux plus fortunés, on roule sur des cyclomoteurs qui en ont à peu près l'aspect, de préférence une Flandria ou une Paloma, une mobylette à la rigueur. La petite délinquance est répandue dans ce milieu, sans être généralisée. Mais afin de choquer, les blousons noirs (qui se nomment eux-mêmes « loulous ») affectent de jouer les durs et de parler des argots empruntés au monde des truands.Ce milieu fournit la base sociale qui sera le marché initial du rock français. Il trouve ses héros en Johnny Hallyday, Eddy Mitchell et spécialement Vince Taylor, avant que la vague yéyé ne relègue au second plan les blousons noirs, à partir de 1963, le tournant a lieu le 22 juin 1963, lors de la « folle nuit de la Nation » : un concert gratuit organisé par Salut les Copains à Paris sur la Place de la Nation attire une immense foule, des incidents graves ont lieu, attribués (à tort ou à raison) à des bandes de blousons noirs. La scène yéyé prend définitivement ses distances avec ces derniers.

Les sociologues qui se penchaient alors sur les origines du problème de la délinquance juvénile évoquaient un conflit de génération ou une révolte contre l'ordre établi, avant d'avancer des facteurs économiques.La thèse la plus courante suggère que les jeunes de tous les pays ayant connu les privations de l'après-guerre se sont lancés à corps perdu dans la recherche de la liberté et le plaisir, voulant jouir immédiatement des biens que la société de consommations leur proposait: musique, moto ou mode. Mais pas assez riche pour pouvoir se les procurer et s'apercevant que la société n'était pas disposée à modifier ses habitudes, ni à ne leur faire aucune concession, ils se révoltèrent et leur enthousiasme se transforma en violence.

D'autres enquêtes au début des années soixante contestent cette thèse en soulignant l'importance de l'urbanisation dans le malaise des jeunes en mettant l'accent sur la concentration de grands ensembles immobiliers dans les villes véritables fabrique de blousons noirs.

"Les cités industrielles sont surtout pathogènes parce qu'elles favorisent les rassemblements de jeunes gens sur un territoire restreint " (109)

Effectivement, les bandes urbaines profilent surtout dans les quartiers abritant des grands immeubles collectifs type HLM ou des groupes d'habitations à bon marché souvent insalubre. Si les blocs HLM marquent un progrès certain par rapport au taudis, l'essentiel y manque trop souvent. La plus part du temps, il n'y a ni jardins, ni espace, ni équipement sportif sans parler de l'absence totale de distraction. Les enfants et les adolescents ont le sentiment d'être en cage et la rue les attire comme un refuge mauvais.

"On ne sait pas quoi faire, racontent des adolescents. Alors on se retrouve et on s'ennuie ensemble "

Parmi les autres facteurs on évoque souvent la carence d'autorité, mais c'est surtout dans la carence du milieu familial qu'il faut rechercher l'origine du drame des blousons noirs ; famille désagrégée, séparations ou divorces, alcoolisme du père.

Pour Henri Joubrel ; la dissociation familiale est la cause essentielle de la conduite asociale d'un nombre grandissant de jeune. Les statistiques montrent que 80 % des jeunes inadaptés sociaux dont on connaît suffisamment l'histoire pour en établir un dossier approfondi sortent d'un foyer dissocié. (111)

Au foyer, ils se sentent mal aimés, les gosses souhaitent la chaleur, ils trouvent le chaos

" Un soir en rentrant chez ma mère elle m'a virée, elle avait un jules " raconte Momo de la bande des Batignolles, après avoir traîné quelques jours dans les rues, le tribunal lui trouvera une famille d'accueil. (112)

" A quatorze ans, je suis parti travailler. Plâtrier. Pourquoi ? Parce que mon père boit et ma mère aussi ". écrit Jean dans Rallye Jeunesse (113)

Ce qui fait dire à un éducateur lyonnais :

" Ce qui déboussole souvent les jeunes, c'est l'impossibilité de prendre leur père pour modèle"

(114)

Si la société cherche les causes du mal dont souffre la jeunesse un autre facteur souvent négligé réside certainement dans le fait qu'ils sont victime de l'incompréhension des adultes. L'emblématique film " La Fureur de Vivre " évoquait déjà ces relations difficiles entre parents et enfant. A la question "mentez--vous à vos parents" posé par un journaliste qui enquête pour un hebdomadaire sur les problèmes de la jeunesse, des jeunes répondent :

" On ne ment pas, on ne parle pas ".

Puis lorsqu'il leur demande : " Que leur reprochez-vous ? ",

ils répondent: " Ils font vraiment une trop sale gueule à table ! " 58 (47)

Dans la même logique , une jeune fille, Raymonde écrit à Rallye Jeunesse

" Ce dont on souffre, c'est de l'ambiance familiale, du manque de vérité, de l'injustice de ce que nous appelons la "vague des croulants" " (116)Dans le conflit adultes jeunes, on assiste même à des faits incroyables comme histoire révélé par l'Humanité ou des jeunes émules des blousons noirs qui pétaradaient la nuit en scooter troublant le sommeil des citoyens de deux patelins ont été tondues par quelques habitants.

" La tête base, le crâne soigneusement tondu, suivant leur chef de fil qui de surcroît avait été dépouillé de son pantalon, plusieurs jeunes gens ont et promené dans les rues de Charly et de Vernaison près de Lyon sous l'œil marqué de la population… " (117)

109 « Les blousons noirs : une société primitive ? » - H.Michel (Directeur du centre de Vaucresson) – J.Selosse (Chargé de recherche au CNRS), In Sciences Avenir N°211, septembre 1964.

110 – « Les blousons noirs : une société primitive ? »

111 – « Mauvais garçons de bonnes familles » Henri Joubrel, Aubier, Editions Montaigne,1959

112 – « Square des Batignoles », Cinq colonnes à la une, 04/11/1960

113 - « Vous avez la parole », in Rallye Jeunesse N°11, février 1960.

114 – « Les garçons sauvage, le blouson noir, une provocateur mais aussi un mal aimé » Le Progrès de Lyon,09/12/1962

115 - "Mauvais garçons de bonnes familles" Henri Joubrel

116 – « Vous avez la parole », in Rallye Jeunesse N°11, février 1960

117 – « Tondeuse pour porteur de blousons », L’humanité, 21 juillet 1961 Si la bande est sociale dans sa structure, elle est par contre anti -sociale par son activité et par sa fonction. Si à l'origine elle ne semble pas se constituer dans un but délinquant, la bande est perçue sous cette forme par la police et la société. En réalité beaucoup de jeunes blousons noirs adoptaient uniquement un mode de comportement sans verser dans la délinquance mais s'exposaient de part ce fait à la réprobation sociale et à la répression. La plupart du temps les actes délictueux ne sont pas prémédités et sont commis dans l'inconscience la plus complète. On cherche surtout à réaliser un coup pour se valoriser sans vraiment se rendre compte de la gravité du délit.

" Ils ne se préoccupent pas exagérément des ennuis qu'ils ont eux avec la justice et ne s'inquiètent pas à l'idée d'avoir un casier judiciaire "(93)

Les Coeurs verts Edouard Luntz (cahiers du cinéma)

Les deux tiers des délits reprochés aux adolescents délinquants sont commis contre la propriété, dont les formes essentielles sont : le vol, les délits visant les deux roues et les actes de vandalisme.

Exemple type de l'activité d'une bande ; celle d'Arpajon dont la police a arrêté le mois de décembre 1959 une vingtaine de membres. Ces garçons âgés de 14 à 18 ans qui suivaient la plupart des cours professionnels dans la région parisienne, se réunissaient chaque jour sur le pont de l'Orge pour y préparer leurs "coups".

" Ils essayaient des blousons en plastique noir et se sauvaient sans les payer. Ils chipaient des disques, pour les écouter ou les revendre. Ils volaient des scooters et des voitures qu'ils abandonnaient hors d'usage. Ils faisaient main basse sur le contenu des autos en stationnement. Ils crevaient les pneus, allumaient des incendies ". (94)

Des adolescents par manque d'argent de poche pratiquent le vol à la tire et certain n'hésitent pas à faire les sacs des veilles dame. Le vol à l'étalage sert des fois pour l'alimentation des surboums. Le vol a parfois l'aspect d'un jeu, d'un défi lancé aux règles sociales.

Les objets volés sont souvent considérés comme des trophées et planqués dans des repaires. C'était le cas pour une bande de Nancy dont les exploits consistaient à voler les objets les plus hétéroclites au cours de cambriolage pour les tenir stockés dans une cave. Le chef de la bande âgé de 16 ans n'a pas hésité à tirer avec une carabine sur les inspecteurs de police venue les arrêter. Ce qui vaudra les assises à trois mineurs. Dans la même région à Charleville, un groupe de six mineurs de 14 et 15 ans connus sous le nom de " La bande des blousons verts " dirigé par un garçon de 20 ans commet 24 vols et cambriolages, le plus souvent la nuit, par effraction. (95)

Dans la région bordelaise chaque membre du gang des As avait son casier dans le garage abandonné qui leur servait de Q.G. on y trouvait les objets les plus hétéroclites, sous-vêtements féminins, couteaux, fer à repasser, boîtes de conserve, appareils photos, jouets, chapelets, rasoirs, statue religieuse etc. Leurs plus beaux trophées; une plaque minéralogique de car de Police Secours qu'ils conservaient jalousement dans leur repaire (96)

Certaines bandes étaient spécialisées dans le casse, lors d'un interrogatoire un jeune raconte avec cynisme ses exploits :

" En pleine nuit, quand nos parents dormaient, on se sauvait et on se retrouvait là... Là, on buvait pour se donner du courage, on s'habillait, on emportait la matraque, et on y allait. On s'habillait tous pareil, avec un masque, pour ne pas être reconnus. Ca commençait par les vitrines des petites veilles. On fait le coup en quelques secondes, à grands coups de matraques. On se donne même pas la peine de voler, ça ne nous intéresse pas... juste une bricole en guise de souvenir. Après le casse on se sauvait en vitesse par des ruelles d'où on n'avait rien pu entendre. On revenait fêter ça et on allait se coucher " (97)

  

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99) Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99)

Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

 

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

« LA SOCIETE NOUS AIME PAS, NOUS LES JEUNES ! »

Serge de la bande du Square des Batignolles (Cinq colonnes à la une 1960)

« Ces adolescents effondrés contre les murs, à la manière des cow-boys des westerns le long des cloisons des saloons, sont capables brusquement de lever le cran d'arrêt de leur énergie. Une poussée irrésistible les portes à imiter le Marlo Brando de l'Equipée Sauvage ou le James Dean de la Fureur de vivre"

Henri Joubrel, Jeunesse en danger, Fayard,1960

 

Les blousons noirs sont un phénomène essentiellement urbain. A Paris chaque porte, chaque quartier prolo possède sa bande. Un article de presse daté de l'été 1959 fait état de six bandes principales à Paris et de 70 autres cliques de moindre importance. (76) Selon la préfecture de police 10000 jeunes fréquentent des bandes dans la capitale. (77)

A l'époque la bande la plus importante de la capitale était celle du Talus capable de regrouper 250 à 300 jeunes le samedi soir. Ceux de la porte de St -Ouen se distinguent par la parfaite maîtrise des diverses langues des voyous. La bande du square des Batignolles et leur chef Pilule sont le sujet d'un reportage de l'émission télé Cinq colonnes à la une en 1960. Tout aussi médiatisée, la bande de la Bastille, forte d'une centaine de membres qui parlait un argot forcé. Une enquête est publiée sur eux l'été 1961 par Christian Magret dans le magazine des têtes couronnées Point de Vue. Le chanteur Moustique membre de ce groupe déclare quelques années plus tard dans un entretien:

" A la fin des années 50, on attaquait un car de flics, on cassait les vitres et on piquait le car pour une virée " (7

La bande du Sactos (Sacré Cœur) tournait aussi autour de la centaine et était protégée par leur curé. Elle était très crainte par les autres bandes. Johnny Hallyday qui faisait partie de la bande du square de la Trinité raconte :

«On jouait les durs. On se battait, mais nous fermions notre gueule lorsque la bande du Sacré-Cœur descendait" (79)

La plupart des bandes se singularisaient en arborant le même signe distinctif, qui allait de la manière de se coiffer, aux différents accessoires ; médailles, voir une tête de mort ou un minuscule couteau retenu au cou par une chaîne, bagues, bracelets ou ceinturons incrustés de pièces de monnaie. Cette singularité se retrouve sur leurs engins à deux roues; mobylettes ou scooters : fanions à tête de mort, hélices en plastique de la même couleur gagnées à la fête foraine. La même décalcomanie collée sur le réservoir ou le garde boue ; photos de Tarzan ou de James Dean, vamp, tête d'indien, trèfle à 4 feuilles. L'accessoire peut donner son nom à la bande, ainsi la bande du Damier d'un port breton arborait un damier sur leurs véhicules.

En 1960, 53 % des jeunes qui fréquentaient les bandes sortaient de familles ouvrières, les fils d'employée représentaient 12%.

A noter que 18 % des effectifs des bandes seraient originaires des milieux sociaux supérieurs.

" La majorité de ces jeunes étaient issue des classes sociales défavorisées bien que la bourgeoisie eut ses blousons dorés. Les bandes constituent une configuration culturelle originale, articulée sur une culture de classe. La culture ouvrière en est le soubassement " (80)

Les adolescents de 15 à 17 ans en constituent le noyau le plus important (53, les plus jeunes de 13 à 14 ans représentent 14,8% des membres et ceux de 18 à 20 ans 18,1 % (81) Les blousons noirs des années 1959-1961 appartiennent à la génération des enfants de la guerre, ceux nées pendant la seconde guerre mondiale entre 1939 et 1945 et dans l'immédiate après guerre.

 

Les bandes tournent généralement autour de trois noyaux. Le noyau central composé de ceux qui étaient le plus en vue, quatre à cinq personnes souvent confrontées à la délinquance. Puis vient la bande proprement dite formée en moyenne d'une quinzaine à une vingtaine de membres qui cherchaient surtout à se faire remarquer. Le troisième noyau qui pouvait être plus important jusqu'à une centaine de jeunes était composé des sympathisants et des postulants qui formaient le halo de la bande présent lors des grandes occasions comme une bagarre entre bandes rivales. La bande forme un milieu homogène, l'embryon en est la "cour " où les enfants d'un même immeuble vivent et grandissent ensemble. Vers l'âge de 12 ans les enfants de plusieurs cours se groupent dans des lieux de rencontre plus vaste : places ou squares où ils se forment en bande. Dans la bande, les adolescents se retrouvent et ne s'expriment qu'en symbiose avec les autres.

Le dynamisme du groupe est contenu dans ses motivations qui portent le jeune à avoir en face de lui des interlocuteurs qui le comprennent, qui ont les même besoins et les mêmes soucis que lui et ne par conséquent être des adultes qu'ils haïssent.

" Les vieux ont s 'en fout, ils peuvent tous crever” répond spontanément un jeune blouson noir au juge d'instruction qui lui parlait de ses parents (82).

Pour son reportage dans l'Express, Jean Cau demande à Jojo de la bande de la Porte de Vanves. " Pourquoi "les vieux" à ton avis ne vous comprennent pas ? " réponse de Jojo : " Parce que qu'on voit la vie autrement ! " " Qu'est ce que tu veux dire ? " lui demande alors l'écrivain. Le blond répond à sa place : " Ils voudraient qu'on porte des gilets, qu'on ait des pantalons comme ça, qu'on soit comme eux ! " (83)

Ensemble, ils reconnaissent être différents des autres, mais cette différence, paradoxalement se manifeste par le maximum de conformité avec ceux du groupe. C'est pour cela que le vêtement, la coupe de cheveux, le langage ont une telle importance, ils manifestent une singularité collective. Mais si la panoplie marque la rupture avec le monde adulte, elle ne devait pas être usurpée. Il faut être reconnu par ses pairs, il y a des modèles, l'orgueil, l'honneur et l'exploit ont une grande place dans la vie des bandes. L'intégration dans une bande n'est pas une chose facile. La bande est une société tellement fermée qu'y pénétrer est incontestablement une victoire. Elle passe par deux étapes, celle de la reconnaissance puis celle de l'acceptation. Pour être accepté, il y a des rites d'admissions. Le postulant doit faire ses preuves en réalisant divers exploits qui pouvaient aller du combat au cran d'arrêt à la course de mobylettes dans les sens uniques ou sur les " fortifs " (Certains tronçons des fortifications de 1870 subsistaient encore dans la capitale à la fin des années 50 (84). Parmi les autres exploits couramment pratiqués ; se battre avec le chef ou piquer une nana dans une bande ennemie. Ces pratiques sont souvent associées avec le rituel du " frère de sang " Le chef du gang entaille avec son couteau l'avant bras du postulant, puis fait la même estafilade en forme de croix sur celui du dernier rentré dans le groupe. Il maintient leur deux bras ensemble, unis par le mélange de leur sang, les deux "frères" jurent que jamais ils ne trahiront leurs camarades. Une autre caractéristique de la bande est le vif sentiment de propriété vis à vis de son territoire. Elle a ses lieux de réunion, ses cafés et ses cinémas et n'en change pas et ne tolère pas qu'une autre bande vienne empiéter sa zone, sinon c'est la guerre. Le square, mini espace de verdure apparaît l'endroit idéal pour leurs rassemblements. Là, les garçons discutent ensemble, se racontent des histoires de filles ou de taules souvent exagérées. Ils s'échangent des idées, blaguent, s'amusent, se chamaillent entre eux tout en écoutant de la musique sur un transistor. Dans ce lieu, où ils traînent souvent tard le soir les adolescents éprouvent un sentiment de liberté.La fête foraine est un autre coin qui les attire, et ils aiment se regrouper autour des auto-tamponneuses. Il y règne une certaine ambiance, adossés à la balustrade, ils prennent plaisir à regarder tourner les voitures en écoutant les derniers disques à la mode ou draguer les filles. L'hiver on se met au chaud dans les salles de jeux avec une prédilection pour le flipper. Au Café, ils ne consomment pratiquement pas d'alcool, préférant le diabolo ou le café crème. Paris, connaît l'hiver 1959 la grande vogue du patin à glace. Les patinoires de Saint Didier ou de la " fédé " de Boulogne sont prises d'assaut par des hordes de gamins.

" La fédérale c'est la roue tournante de tous les blousons noirs, on retrouve les copains de tous les quartiers. Il y a des filles, ce n’est pas cher et on s'amuse bien " raconte Pilule chef de la bande des Batignolles (85). Quant au bal, ils y vont très rarement la plupart de ces garçons ne savent pas danser, mais sur place ils aiment bien provoquer des bagarres.

" Le soir d'une fête patronale une quarantaine de jeunes venus de Rouen à scooter, à cyclomoteur ou en taxi, avaient plusieurs fois tenté de pénétrer dans la salle de bal en refusant de payer. L'expulsion par les gendarmes de deux ivrognes leur fournit le prétexte recherché pour passer aux actes de violence. Toute la bande se rua alors sur les représentants de l'ordre et l'un des gendarmes fut roué de coups. Son collègue tira quelques coups en l'air. Ce geste décontenança un temps les agresseurs mais les gendarmes partis, les jeunes gens pénétrèrent en force dans la salle où il brutalisèrent plusieurs danseurs et plusieurs femmes "(86)

Les bandes importantes comportent parfois un tiers de filles. On y trouve souvent des filles garçons qui rêvent d'être des garçons et se conduisent comme tels. Elles revendiquent leur égalité dans les comportements antisociaux et le manifestent notamment par des attitudes de bravades vis à vis de la police lorsque celle-ci intervient. Le journal le Progrès de Lyon raconte le comportement de deux filles membres d'une bande du quartier de Perrache après leur arrestation :

"On reste confondu lorsque l'on sait que ce sont les deux filles qui tinrent tête avec le plus d'aplomb au commissaire et firent preuve d'une inconcevable impolitesse. L'une se contenta de dire : "Je me fous de la police, je me fous de la famille" L'autre, encore plus effronté, n'alla-t-elle pas jusqu'à déclarer : " Parlez moins fort. Vous me faites mal aux oreilles…" (87)Mais la majorité des adolescentes qui fréquentent les bandes peuvent être classées dans la catégorie des "filles-objets" guère respectée qui servent à l'initiation sexuelle des garçons. Elles vont d'un garçon à l'autre, et prennent une sorte de valeur marchande en se faisant échanger pour trois fois rien! Il y aussi les filles attitrées que possèdent les principaux membres de la bande, qui souvent par prudence sont rarement vues par les autres gars. Les filles participent rarement aux délits, mais en sont les complices indirectes en bénéficiant souvent en forme de cadeaux des produits dérobés. Elles aiment se faire conduire dans des véhicules volés, ce qui donne un certain prestige à l'auteur de l'acte délictueux. La délinquance est souvent un moyen de se poser en homme devant la femme pour obtenir ses faveurs. Si quelques séries B américaines de la fin des années cinquante ont fait des gangs de filles l'un de leurs thèmes favoris. L'existence de quelques bandes féminines en France a été confirmée par certains enquêteurs. Lorsque le journal La Montagne évoque une agression commise par une bande de jeunes filles à Caen, on emploie symboliquement le terme de "jupons noirs" : "Les jupons noirs de Caen rouent de coup un Nord-Africain" (8 On note surtout une délinquance féminine opérée en petit groupe dans les grands magasins. Une fille achète un produit pour occuper la vendeuse, une autre fait le guet, tandis que la troisième vole des vêtements ou des aliments. Comme dans l'histoire du film de Marcel Carné " Terrain Vague " on signale des gangs de garçons dirigés par une fille. Exemple, le gang des As une bande délinquante de la région bordelaise qui avait à sa tête Berthe une gamine de 16 ans. (89)

Terrain Vague

Le rapport au travail du blouson noir est complexe. Le gars qui à l'habitude de vivre en bande n'a pas envie de la quitter pour aller bosser, tandis que celui qui travaille de voir ses copains traîner toute la journée lui donne des mauvaises idées et il s'arrête de travailler. Le marché de l'emploi de l'époque le permettant, on travaille selon l'envie ou la nécessité.

" Si le gars travaille, un moment, pendant une semaine ou un ou deux mois, c'est qu'il a besoin d'argent pour s'habiller, pour manger, pour s'acheter une mobylette. Ou bien c'est qu'il s'est produit un renversement moral: son instinct est devenu faible et sa volonté lui a permis de travailler pendant ce temps là " (90)

" Je travaille quand j'ai besoin de fric. S'il me faut une paire de " groles ", je fais la plonge. Si c'est une nécessité plus grave, je me fais embaucher un mois ou deux dans mon métier" . Raconte Guy 18 ans (91)

Les contrats d'apprentissages sont la plupart du temps des contrats pour la forme. Les patrons en profitent pour mal payer les jeunes, mais ils les font travailler comme des ouvriers adultes. En plus, les jeunes apprentis supportent mal les ordres des chefs d'équipes, de ce fait, ils changent régulièrement de métier. Le plus souvent les jeunes des bandes qui travaillent exercent des métiers sans grande qualification comme: télégraphiste, plombier, graisseur. Des métiers où la main d'œuvre est variable qui leur permet de changer de patron, de lieu de travail à leur guise. Lorsqu'on demande à Moustique le benjamin de la bande de la Bastille qui ambitionne de trouver un boulot " pépère " quel genre de travail il aimerait faire, il répond: " Ben : aide routier, livreur en triporteur ou alors être le fils de taulier, avoir une carte de figurant de cinéma ".(92)

 

76 – Philippe Macaigne "Quelques réflexions sur la présentation de la presse écrite des "blousons noirs", in Annales de Vaucresson, N° 2,1964

77 - C.Freinet, « La formation de l’enfance et de la jeunesse », Edition l’école moderne, 1960

78 - Interview Moustique par Christian Victor in Juxe-Box Magazine N° 86, novembre 1994

79 - Interview Johnny Hallyday par Jacques Barsamian in Juke Box Magazine N° 42, novembre 1990

80 - Jean Charles Lagrée in "Les jeunes chantent leurs cultures", page 19,L’Harmattan , 1982

81 - Rapport annuel de l’Education surveillé pour 1960 in "Les bandes d’adolescents","Les classes d'age" page 3 Philippe Robert, Pierre Lascoumes Les éditions ouvrières,Paris 1974

82 - "Les vieux ? qu'ils crèvent ! « Le mal de la jeunesse » ,in Faim & Soif N°33, 7/02/1960

83 - Jean Cau, Les gosses révoltés, l'Express 30 juillet 1959

84 - Long Chris "Johnny", page 17,J'ai Lu N°2380,

85 - "Square des Batignoles" Reportage de Pierre Dumayet, Cinq colonnes à la une,4/11/1960

86 - « Quand la jeunesse faisait peur », Laurent Mucchielli, chercheur au CNRS

87 - "Des blousons noirs sont surpris dans leur repaire par les policier" in Le Progrès de Lyon, 22 mai 1962

88 - La Montagne, 18 juin 1960, Claire Bacher 3Le phénomème bmousons noirs vu par la presse Maitrise faculté de Clermont Ferrant 2000

89 -Philippe Parrot, Monique Gueneau "Le gang des As" in "Les gangs d’adolescents",PUF,1959

90 - in "Cri d'appel d'un blouson noir", page 47, Fayard, 1962

91 - In “tribune libre des jeunes” Cinémonde 16/10/62

92 - in "Les Blousons

 

Blousons noirs. Soixante ans après, l’expression a gardé toute sa force évocatrice, porteuse d’une mythologie cuir mêlant violence et rock’n’roll naissant sur fond de désœuvrement et de misère sociale (ça ne vous rappelle rien ?). Le festival Filmer la musique, que Poptronics suit quotidiennement, y consacre une journée entière avec deux films, une séance de documents d’actualité d’époque et un concert de Magnetix en clôture au Point Ephémère.

1955, « Graine de violence » (« Blackboard Jungle ») sort au cinéma. C’est l’émeute : la jeunesse française découvre en même temps les déhanchements de Presley et le « Rock Around The Clock » de Bill Haley. Les choses ne seront plus tout à fait pareilles : le rock’n’roll vient d’entrer dans la culture populaire hexagonale. Et avec lui, ceux qu’on appelle encore les « tricheurs », d’après le titre du film de Marcel Carné qui sort en 1958, ces jeunes banlieusards des cités qui sortent de terre. Il y a déjà eu quelques gros incidents : à l’été 1955, un concert de Louis Armstrong déclenche une bataille de trois jours dans les rues de Paris, en octobre 1958, le concert de Bill Haley à l’Olympia donne lieu à des débordements : des fauteuils sont détruits par centaines.

  

Mais c’est à l’été 1959 que la France découvre, tétanisée, les blousons noirs. Le 24 juillet, vingt-cinq jeunes de la Porte de Vanves déboulent dans le XVe arrondissement pour affronter la bande du square Saint-Lambert, vêtus de blousons de cuirs, de jeans, et armés de chaînes de vélo. Le lendemain, on se bagarre à Bandol pour une histoire de filles. Quelques jours plus tard, un policier est blessé à Cannes lors d’affrontements avec une bande de Courbevoie. L’affaire fait la Une (« Un agent de police a été sauvagement poignardé par une horde de tricheurs, de blousons noirs »). Les incidents se multiplient tellement (à la sortie de « Jailhouse Rock » en 1960, le cinéma Le Mac Mahon est littéralement pris d’assaut) que le sinistre Maurice Papon, préfet de police de Paris depuis 1958, songe très sérieusement à interdire le rock’n’roll pour préserver la « tranquillité publique ». Cette peur diffuse de la jeunesse, on la retrouve dans les reportages de l’ORTF,

 

Revenir en haut Aller en basDans quel contexte apparaissent les blousons noirs ?

C’est de la délinquance sur fond de rock’n’roll, de guerre d’Algérie et surtout de naissance des cités. A l’époque, face aux barres de Nanterre, La Défense est un immense terrain vague sur lequel seul le Cnit est construit. A peine sortie de terre, cette urbanisation est déjà porteuse de problèmes et provoque désœuvrement, ennui, marginalisation. Il ne fallait pas être visionnaire pour voir que ça allait être le bordel : l’environnement, c’est déjà celui de « Ma 6-t va crack-er ». Cette jeunesse ouvrière qui traîne en bas de ces grandes barres HLM nickel s’emmerde et se radicalise. Les blousons noirs terrorisent les gens, ils niquent toutes les nanas, qui toutes veulent être niquées par eux ! Ils n’ont pas de conscience politique, pas vraiment de conscience sociale non plus, ils sont dans l’énergie brute : ils foutent le bordel et c’est tout.

Quand le mouvement devient-il massif ?

Quand Hallyday débarque, en 1961. C’est un choc. Jusqu’alors, le business de la musique est aux mains de vieux qui se projettent sur les envies des jeunes et suivent les modes. On a affaire à des orchestres de bal qui jouent du twist, quelques mois plus tard ils font du cha-cha ou du calypso. Hallyday, lui, fait de la musique pour les jeunes sans une once de cynisme. Et ça, les kids, ça leur fait péter les plombs. Quand Johnny ou Vince Taylor jouent à l’Olympia au début des années 60, ils cassent tout, ça fait la Une des journaux, avec des slogans choc, ça fait flipper tout le monde car cette expression de la violence des jeunes en groupe est assez nouvelle. Les blousons noirs succèdent en quelque sorte aux apaches du début du siècle, qui eux étaient vraiment dans le banditisme. Là, ce sont des branleurs. C’est assez inédit.

C’est une esthétique aussi...

Oui, les blousons en cuir, les jeans, on est complètement dans le fantasme du motard, de « L’Equipée sauvage ». Brando, avant James Dean, devient une véritable icône de cette jeunesse. Il y a un côté désuet à les revoir aujourd’hui, un mélange de pathétique et de sublime. Le phénomène est assez européen, très présent en Suisse, en Allemagne, mais en France, c’est quelque chose de dur, le cuir, les chaînes, il y a une volonté d’effrayer le bourgeois, de faire peur, un vrai désir de choquer et de provoquer. Aux Etats-Unis, on ne trouve pas tous ces atours, tout cet apparat.

Les blousons noirs disparaissent peu à peu au cours des années 60. C’est la fin du rock’n’roll dans les cités ?

Difficile de dater la fin du mouvement, beaucoup rentrent dans le rang assez vite (selon quelques rares études, plus de la moitié des blousons noirs ont entre 14 et 17 ans, huit sur dix ont moins de vingt ans, ndlr), une petite frange tombe dans la vraie marginalité. Mais le rock ne disparaît pas pour autant du paysage banlieusard. Le rock’n’roll n’a quitté les cités qu’avec l’arrivée du rap. Jusqu’au début des année 80, tout le monde y écoute du rockabilly et du rock’n’roll, qu’on soit blanc, black ou arabe. Gene Vincent est une star des cités. D’ailleurs, ceux qui ont fondé les premiers labels de rap étaient tous d’anciens fans de rockabilly. La naissance des blousons noirs La bande de « Titine » au pied des HLM du Pré-Saint-Gervais. 'agression du jeune Yuriy, en janvier dans le X Ve arrondissement de Paris, a mis en lumière les affrontements entre bandes. Mais à la fin des années 1950 déjà les héritiers des Apaches de la Belle Epoque n’avaient peur de rien ni de personne. Ils aimaient la castagne, les Mobylette et le rock’n’roll. Immersion chez ces petits voyous du Pré-Saint-Gervais, avec le photographe André Lefebvre. La vague est partie des Etats-Unis. Leurs références sont James Dean et sa « Fureur de vivre », Brando dans « L’équipée sauvage ». Partout, ce sont les mêmes jeunes en proie au même mal du siècle. En Angleterre , on les appelle les « Teddy boys », en Allemagne les « Halbstarken », en Suède, les « shunna folke », en France ce sont « les blousons noirs ». L’expression est lancée par le journal « France-Soir », à l’été 1959, après un affrontement entre bandes, square Saint-Lambert, dans le XVe arrondissement de Paris. Avec leurs manteaux de cuir, leurs cheveux mi-longs gominés, leurs chaînes de vélo et leurs poings américains, ils se rassemblent au pied des tours ou des pavillons aux façades décrépies, dans les quartiers populaires des villes ou de leur périphérie. La plupart du temps, les blousons noirs appartiennent à la classe ouvrière, vivent de petits boulots et grandissent dans des familles éclatées. Ils sont les laissés-pour-compte des Trente Glorieuses marquées par l’essor économique et l’émergence de la classe moyenne. Dans le groupe du Pré-Saint-Gervais qu’ont suivi Jean Maquet et André Lefebvre, les journaliste et photographe de Match, la moyenne d’âge est de 16 ans. « Ces jeunes gens sont tout au plus égarés, ils ne sont pas vicieux. Ils vivent en bandes, certes, mais ce mot de bande est trompeur. On pense aux bandes de gangsters, écrit Jean Maquet [...]. Les membres des bandes de blousons noirs, dans l’immense majorité des cas, ne sont que des copains. Il faut insister sur ce point. Il serait on ne peut plus néfaste, et pour tout le monde, que le public se fasse du blouson noir une idée trop noire [...]. Le problème des blousons noirs est grave : il n’est pas encore tragique. » Des copains qui inventent leur propre culture, de nouveaux codes.

Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes @ Sur leurs postes de radio, ils écoutent le rock’n’roll d’Elvis Presley ou de Vince Taylor. Très loin des yéyés. « Ils ont besoin de se sentir virils », écrivait le journaliste de Match. « Cela donne la baston, c’est-à-dire le règlement de comptes à mains nues entre hommes, et, de temps en temps, la “frite”, c’est-à-dire la bagarre générale [...]. Bref, la violence. » Une violence gratuite, pour passer le temps, par exubérance juvénile, par désir de se montrer brave. On se bat pour s’imposer, prendre le pouvoir dans le quartier ou juste pour la gloire, on se tape des virées dans des voitures volées… Ils commettent des larcins, pillent ou cassent plus par défi que par besoin ou conviction. Et, s’ils brandissent leur haine des « flics » et de l’ordre bourgeois, ils ne défendent aucune cause. Leur conscience politique ne ressemble en rien à celle des étudiants de Mai 1968 qui crieront leur révolte quelques années plus tard. Malgré leur rejet de l’autorité, les bandes sont hiérarchisées autour du chef et de ses lieutenants, qui ont tous un surnom. Pour en être, il faut respecter certains rituels, être initié, savoir se montrer téméraire, commettre un vol ou se mesurer à un rival. La presse, qui s’est emparée du phénomène, en fait un mythe. Un congrès sur la délinquance juvénile est même organisé en Italie. Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes. Parmi eux, 45 000 ont moins de 18 ans. Comme les loubards ou les jeunes des cités après eux, ils veulent s’affirmer, interroger la société, la provoquer, mettre à l’épreuve sa capacité à les intégrer. En marge, cette jeunesse défavorisée est gangrenée par le désœuvrement. « Sur ce point, ils sont unanimes. Ils s’ennuient, écrivait Jean Maquet. Ils sont incapables de rester seuls. La bande, cette bande fluctuante, c’est ce qui les délivre de leur solitude, leur donne l’illusion d’une fraternité et sans doute, pour beaucoup d’entre eux, d’une famille. Ils ne lui en demandent pas plus. » 69 VENISSIEUX Les MJC 1959-1981 De l'été des blousons noirs à l'été des Minguettes Broché – 3 avril 2008 Les Maisons des jeunes et de la culture (MJC) font partie de ces institutions méconnues bien que souvent évoquées. Parfois confondues avec les Maisons de la culture d'André Malraux, parfois assimilées à de simples maisons de jeunes, elles sont victimes de l'ampleur de leur objectif : lier jeunesse et culture dans une perspective d'éducation populaire. Ce livre retrace leur histoire à leur apogée, entre 1959, lorsque la médiatisation du phénomène blousons noirs favorise une mobilisation en leur faveur, et 1981, quand l'apparition du " mal des banlieues " signalait un changement d'époque : l'insertion sociale des jeunes devenait une priorité tandis que le lien entre jeunesse, loisirs et action culturelle achevait de se dissoudre dans la crise du socio-culturel. Entre ces deux dates, le millier de MJC que comptait alors le territoire a connu une histoire aussi riche que mouvementée. La diversité des activités abritées dans leurs murs n'a d'ailleurs pu que contribuer à rendre les MJC difficilement saisissables : tour à tour foyers de jeunes et maisons pour tous, proposant expérimentations théâtrales et ateliers de bricolage, espaces de débats et sociabilité, elles furent aussi des pépinières pour la formation de militants culturels et politiques locaux. Lieux singuliers qui ont pu être présentés, parfois simultanément, comme des repaires de gauchistes, des centres de propagande communiste et des terreaux de la deuxième gauche, les MJC permettent de saisir la complexité de la vie associative, dans sa richesse mais aussi sa difficulté. Voilà un très beau livre de synthèse sur un sujet qui ne peut manquer d’intéresser les lecteurs de cette revue. Même si les MJC (Maisons des jeunes et de la culture) n’avaient pas pour finalité de contribuer à la lutte contre la délinquance, elles ont été parfois perçues par les municipalités comme un des outils efficaces de prévention, en particulier à l’époque des blousons noirs. Le sous-titre adopté par l’ouvrage rappelle d’ailleurs cet impact possible ou souhaité sur la prévention. Mais Laurent Besse a bien d’autres ambitions ici, et il analyse les MJC à l’aune de l’éducation populaire, et de ses grandes ambitions au lendemain de la Libération. Il les suit donc depuis la République des jeunes, dont l’idée est née au sein du gouvernement de la France libre à Alger (d’après leur fondateur André Philip), jusqu’à l’arrivée de la gauche au pouvoir. En fait, il commence surtout avec leur très forte expansion sous le régime gaulliste avec la nomination de Maurice Herzog, fin 1958, comme haut-commissaire à la Jeunesse et aux Sports. La préface d’Antoine Prost souligne d’ailleurs le paradoxe des MJC : ce sont des institutions de gauche surtout présentes dans les villes de droite et du centre, et Laurent Besse montre que les MJC bénéficient avec Herzog d’un appui essentiel. En 1965, lors de l’anniversaire de leurs vingt ans, la fédération des MJC compte trois fois plus de maisons qu’en 1959. Deux autres paradoxes, soulignés par Antoine Prost, caractérisent les MJC. Elles sont laïques, mais mal vues de la Ligue de l’enseignement. Elles sont destinées aux jeunes, mais accueillent bien d’autres classes d’âge.

2Issu d’une thèse soutenue à Paris-I en 2004, ce livre repose sur une abondante documentation, permettant d’analyser les réactions du tissu local comme les enjeux nationaux, la sociologie des directeurs autant que la philosophie des fondateurs, les pratiques de loisirs autant que les ambitions culturelles. Si les archives de la fédération FFMJC (Fédération française des maisons de jeunes et de la culture), et de la fédération concurrente UNIREG (Union des fédérations régionales de MJC) à partir de 1969, ont été essentielles, elles ont été heureusement complétées par celles des douze principales fédérations régionales, et celles des MJC de quelques grandes villes (Châtellerault, Grenoble, Orléans) ainsi que de fonds privés de militants. L’ouvrage est donc parfaitement étayé, foisonnant de précisions qui en rendent la lecture vivante, et qui n’effacent jamais le souci d’une réflexion synthétique.

3Le livre est bâti sur une chronologie fine, qui distingue trois périodes au cours de ces deux décennies, qui ont vu la multiplication des MJC et leur ouverture à un public élargi. Les 14-21 ans y sont majoritaires dans la décennie 1960 (cf. la première partie « Des maisons pour les jeunes - 1959-1965 »), recrutés parmi les « inorganisés », qui n’appartiennent à aucun mouvement, et dont on souhaite qu’ils viennent aussi bien du monde des ouvriers (les travailleurs manuels), que des étudiants (les lycéens). Le projet des initiateurs des MJC (et l’auteur insiste sur le portrait d’André Philip et de sa philosophie de laïcité ouverte) est d’ouvrir une maison de loisirs culturels et éducatifs pour cette classe d’âge, tous milieux sociaux confondus. Le pari est tenu, en particulier autour des activités de ping-pong et de judo.

4La deuxième partie (« Maisons contestées ? Maisons de la contestation ? 1966-1969 ») insiste sur le choc qu’a été pour la fédération des MJC le départ de Maurice Herzog et son remplacement par François Misoffe, devenu ministre de la Jeunesse et des Sports, hostile aux animateurs et décidé à étouffer ces maisons de la contestation et à les remplacer par « mille clubs » beaucoup plus légers. La fédération est déstabilisée et même si le projet ministériel de suppression de la FFMJC échoue, André Philip démissionne. La FFMJC a fait figure d’administration parallèle et cela ne pouvait pas laisser le pouvoir gaulliste indifférent. C’est le moment aussi où les MJC s’ouvrent aux débats et, sans être le fer de lance de la contestation en 1968, s’en font la caisse de résonance.

5L’interrogation sur « Des maisons pour tous (1970-1971) » qui structure la dernière partie, repose sur le fait que les MJC accueillent alors un public nouveau, de femmes et d’enfants, relativement inconnu jusqu’ici, que l’animateur militant laisse la place peu à peu aux vacataires compétents. Elles deviennent des maisons de loisirs pour tous, et des lieux d’une autre culture, avec multiplication de débats sur les marges et les luttes de tous les peuples. Elles accueillent des chanteurs compositeurs débutants et créent des spectacles appelés à circuler. À la fin des années 1970, la mise en cause du socioculturel est l’enjeu de débats passionnés, et le développement de la crise amorce la réflexion sur l’insertion économique des jeunes autant que sur leur développement culturel. Mais les MJC ne sont pas les seules sur ce terrain…

6Tout au long de l’ouvrage est tenu le fil de la réflexion sur l’éducation populaire, sur ses objectifs, ses contenus, depuis l’ambition des origines, jusqu’aux crises mettant en cause la survie même des MJC, aux prises avec les politiques locales et nationales. Comment développer l’éducation populaire ? Comment intégrer ceux qui refusent la participation régulière aux ateliers, préférant les rencontres informelles du foyer autour du baby-foot ? Comment faire coexister les « intellectuels » avec les autres ? Comment, sans exclure, désamorcer les agressivités, les déprédations ? Le livre aborde l’émergence du métier d’éducateur, qui s’est faite précisément au sein des MJC, dans un milieu qui a longtemps préféré le terme de « directeur » (même en pleine affirmation de la non-directivité des années post 68) à celui d’animateur. Comment les recruter, comment les former ? Il insiste sur le fait que les MJC ont été des équipements discrets, à la différence des maisons de la culture, qui, par comparaison, s’affirmaient dans le paysage urbain comme temples de la culture.

7L’analyse culturelle est étroitement imbriquée dans l’analyse des politiques nationales de la jeunesse, mais aussi des politiques locales. La position originale des MJC qui sont des associations 1901 cogérées avec les municipalités, si elle fournit une initiation à la vie démocratique, est aussi source de conflits avec les municipalités. La place du parti communiste, souvent surestimée, fait des MJC des lieux inquiétants pour les élus de la droite, bien que certains, dans bien des villes, leur soient restés fidèles, sensibles à la qualité de leur travail. La comparaison avec les centres sociaux, beaucoup plus marqués par les militants JOC, en fait ressortir la spécificité essentielle dans une jolie formule. Pour Laurent Besse, le centre social, c’est « l’espace des poussettes », alors que la MJC est « l’espace des mobylettes ».

8La conclusion de Laurent Besse est sévère. Pour lui, l’action des MJC se solde par un relatif échec, dans la mesure où elles n’ont pas été capables de s’adresser en masse aux jeunes. Certes, elles ont été les fruits d’une très grande ambition qui aurait pu faire d’elles, sous la IVe République, ce que les maisons d’école avaient été à la IIIe, et des éducateurs populaires, les nouveaux instituteurs de la République. Certes, elles ont bénéficié de la crise des mouvements d’action catholique. Néanmoins, leur projet de devenir le banc d’essai de la citoyenneté, d’être écoles de la démocratie, n’a pas abouti. L’auteur souligne cependant l’offre qu’elles ont apportée à nombre de petites villes et de villes de banlieue, qui seraient restées des déserts culturels sans elles. Mais leur humanisme polyvalent, qui voulait que l’homme complet soit initié à toutes les disciplines, a cédé devant la spécialisation de la vie associative. En outre à la fin des années 1970, l’heure n’était plus à l’animation, mais à l’insertion professionnelle des jeunes. Et Laurent Besse de conclure sur les difficultés actuelles des MJC, à replacer dans « le contexte de déclin de la ferveur éducative, peut-être de l’utopie éducative ».

Haut de page

Pour citer cet article

Référence papier

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière », 12 | 2010, 256-259.

Référence électronique

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière » [En ligne], 12 | 2010, mis en ligne le 21 juin 2012, consulté le 27 juin 2021. URL : journals.openedition.org/rhei/3212 ; DOI : doi.org/10.4000/rhei.3212

Haut de page

Auteur

Dominique Dessertine

Articles du même auteur

Histoire de l’éducation populaire (1815-1945). Perspectives françaises et internationales [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 22 | 2020

Ces êtres intéressants et infortunés : les enfants trouvés des Basses-Alpes au XIXe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 20 | 2018

Droits des enfants au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 19 | 2017

L’œuvre de secours aux enfants et les populations juives au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 18 | 2016

Jean-Pierre Méric, Les pionniers de Saint-Sauveur : la colonie agricole du Médoc pour les enfants trouvés (1844-1869) [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 16 | 2014

(Lecture de) Des enfants venus de loin. Histoire de l’adoption internationale en France [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 15 | 2013

Tous les textes...

Some facts about House Fly:

 

The average housefly lives for 21 days.

 

A housefly can only ingest liquid material. They regurgitate their food to liquefy the food that they are going to eat.

 

A house fly's feet are 10 million times more sensitive than a human tongue.

 

Houseflies are major carriers of disease. They are known to transfer over 100 pathogens, including typhoid, tuberculosis, cholera and malaria. Houseflies collect these pathogens on their legs and mouths when feeding on feces, trash and other decaying material.

 

Flies have over 4,000 lenses per eye (they only have 2 eyes).House fly eyes can recognize even the slightest movements in a full, 360-degree spectrum. This allows the fly to see a far wider range, as well as detect and react to movement at a quicker pace than species with simple eyes. This is the reason that it is extremely difficult to swat a housefly. One tactic that may prove successful is to swat at the fly simultaneously with two objects: this confuses the receptors of the housefly.

 

House flies walk upside down using glue-oozing toe pads

 

If a house fly spots a group of flies, he will join them. That's why granny's sticky fly paper worked so well - a few flies got stuck and soon all the others were rushing over to check out the crowd.

 

Flies lay up to 3,000 eggs in their lifetime of one month.

 

Flies only have 2 wings. Most insects have 4. Their wings beat up to 200 times per second and they stop immediately when their feet land.

 

Follow me @ Twitter | Facebook

 

The Red Knot is a migratory shorebird that travels up to 20,000 km twice a year from its breeding grounds on the high Arctic tundra to its southern non-breeding sites. Along with having one of the longest total migrations of any bird, some populations also fly as much as 8–9,000 km between stopover sites in a single flight. As a shellfish-eating specialist avoiding pathogen-rich freshwater habitats, the Red Knot relies on the few large tidal flats with abundant food resources that the world has to offer. To undertake the physiologically demanding flight from West Africa to northern Siberia, for example, Calidris c. canutus refuels during three weeks of fast feeding in the national parks of the European Wadden Sea. After nearly doubling its weight, it burns off fat stores during the 3 or more days of non-stop flying. The Porsanger fjord in Northern Norway is beside Iceland the most important spring staging area (refueling site) for Calidris canutus islandica on their way from the Wadden Sea to Northern Greenland and North-East Canada.

 

For any form of publication, please include the link to this page:

www.grida.no/resources/1556

 

This photo has been graciously provided to be used in the GRID-Arendal resources library by: Peter Prokosch

A dead muscoid fly (most likely Muscidae), killed by, and exuding spores of, an Entomophthora fungus (Class: Zygomycetes, Order: Entomophthorales).

 

Order: Entomophthorales

Obligate insect fungal pathogens that feed within the live host until all the resources are spent, thereby killing the insect - at which time the fungus must sporulate to infect new living hosts. They produce short term infecting spores (conidia) under favourable conditions (eg. good humidity) and long term hardy resting structures such as chlamydospores when conditions are not favourable. The resting structures will produce conidia when favourable conditions return. Entomophthora muscae is a well known species of this order that attacks the common housefly.

 

Entomophthora muscae

Infecting spores attach themselves to the fly's cuticle, penetrate it to reach the hemocoel (this is the common method of entry for insect pathogenic fungi), and then the fungus will grow within using the fly's nutrients (favouring the abdomen). When the fly dies, 5-8 days later, the white conidia will begin to disperse from between the abdominal segments within 3 hours and continue to do so for the next 10-21 hours.

 

Odd Behaviours and Lures

This fungus has fascinated me, especially for the way it is reported to hijack host behaviour and to set lures for potential hosts - both very successfully serving it's own greater good.

 

You'll notice in the photo above that the fly has died in a peculiar position. Infected flies will die in high positions, on the underside of overhanging objects, and with wings and legs outstretched - such positioning just prior to death is also observed for many other insects lethally infected with similar fungi. It is thought that this odd host behaviour rewiring by the pathogen increases successful spore dispersion and infection, especially of aerial insects.

 

Another trick Entomophthora muscae play to ensure greater spread through host populations is to make the dead female highly attractive to males. It has not yet been determined how the fungus achieves this but male flies who happen upon a sporulating female cadaver have no power to resist it and will immediately engage in "extensive courtship". Hence, potentially becoming infected themselves or even carrying infecting spores to another mate.

 

The Co-evolutionary Battle Heats Up

Flies invaded with Entomophthora fungi have clearly demonstrated 'behavioural fever' whereby they deliberately seek, and bask, in heats above 40 degrees Celsius in the first days of infection. The high raising of body temperatures acts to suppress the pathogen. The obvious benefits of fever are an increase in the onset time of the disease giving the fly a greater chance to complete it's lifecycle and thus pass on this beneficial trait. Fever therapy has also been observed in infected grasshoppers and caterpillars resulting in reduced mortality rates. So should you find your pet house fly 'liaising' with an infected dead fly, a program of sauna therapy is highly recommended.

 

References:

Interactions between fungal pathogens and insect hosts. AE Hajek & RJS Leger. Annual Review of Entomology, 1999, vol. 39, pp. 293-322.

 

Effect of the entomophathogenic fungus, Entomophthora muscae (Zygomycetes: Entomophthoraceae), on sex pheromone and other cuticular hydrocarbons of the house fly, Musca domestica. L Zurek, DD Watson, SB Krasnoff & C Schal. Journal of Invertebrate Pathology, 2002, vol.80, pp. 171-176.

 

Bizarre interactions and endgames: entomopathogenic fungi and their arthropod hosts. HE Roy, DC Steinkraus, J Eilenberg, AE Hajek & JK Pell. Annual Review of Entomology, 2006, vol. 51, pp. 331-357.

Pathogen: Fungal, poss. Bipolaris sp.

Malaria, Leprosy, Tuberculosis, Cholera, Strep, Diphtheria, Syphilis, Gonorrhea, Typhoid Fever, Polio and lots of others just as nasty.

 

Here's a gorgeous 6" x 9" antique lithograph of some of the most deadly pathogens known to man in the last century.

 

This amazing German medical illustration is just one of several harvested from a collection of simply amazing chromolithograph illustrations from the turn of the century.

  

I believe this is Ganoderma zonatum, the pathogen that causes "butt-rot fungus" in palms. This is one of several basidiocarps on the base of a freshly-dead cabbage palm (Sabal palmetto). The fungus effects the lower portion of the trunks, hence the common name. There is no prevention or cure at this time.

Here a link to more information (T.M.I.):

edis.ifas.ufl.edu/pp100

Pathogen: Fungal, poss. Bipolaris sp.

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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

F1K9 Canine Trainer / Instructor Bryan Bice with agricultural disease Detection Dog (in-training) Kos (Vizsla dog) at their training field with U.S. Department of Agriculture (USDA) Agricultural Research Service (ARS) scientists from the U.S. Horticultural Research Laboratory, in Fort Pierce, FL, to train dogs to detect huanglongbing (HLB; a.k.a. citrus greening) in citrus, squash vein yellowing virus (SqVYV; cause of viral watermelon vine decline) in squash, and tomato chlorotic spot virus (TCSV) in pepper plants at this training session in New Smyrna Beach, FL, on Feb. 25, 2021.

F1K9, a licensed canine detection service company.

 

When a dog detects - smell - a diseased plant, its response is to sit or lie facing the plant until it is rewarded with a few seconds of play.

 

Dogs can be trained to detect specific bacterial or viral pathogens in any part of a plant with greater than 99% accuracy, significantly faster than laboratory tests, and before visible symptoms are obvious. Conventional analysis typically uses only one leaf from a plant. At the early stages of infection, before the disease spreads throughout the plant, a healthy leaf may be taken from an infected plant resulting in a negative laboratory test. In contrast, dogs sample the entire plant while walking by and sniffing it. For more information, please go to ars.usda.gov/news-events/news/research-news/2020/trained-dogs-are-the-most-efficient-way-to-hunt-citrus-industrys-biggest-threat/. USDA Photo by Lance Cheung.

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

_-----------------------------------------

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

——————————————————————————

(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

  

-------------------------------------------------- ---------------------

    

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)

_-----------------------------------------

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

——————————————————————————

(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

  

-------------------------------------------------- ---------------------

    

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)

_-----------------------------------------

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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

Les blousons noirs sont une sous-culture juvénile apparue en France dans les années 1950 et qui a connu son apogée entre 1958 et 1961. Issue de l'influence américaine, connotée à un code vestimentaire particulier et au rock'n roll, elle a été la matrice originelle du mouvement yéyé et de quasiment toutes les modes adolescentes ultérieures. Des sous-cultures similaires ont fleuri au même moment dans d'autres pays d'Europe.

La culture « blouson noir » s'est cristallisée autour d'importations américaines qui ont été autant de chocs culturels :

Le film L'Équipée sauvage (The Wild One), sorti en 1953 aux États-Unis mais popularisé courant 1955 en Europe, où le personnage interprété par Marlon Brando révèle d'un coup une façon d'être qui fait époque : cuir noir, moto, machisme, volonté de choquer, esprit de gang, violence à la limite de la criminalité.

Un autre film, La Fureur de vivre (Rebel Without a Cause) arrive en 1956 en France et fait de James Dean une icône définitive. Il introduit l'idée importante que le comportement des (futurs) blousons noirs n'est pas seulement un choix délibéré mais procède d'une fatalité générationnelle et de l'incompréhension des adultes.

L'arrivée au même moment du rock'n roll (Bill Haley et Elvis Presley en premier lieu, puis Gene Vincent, Eddie Cochran etc.) ajoute le son à l'image. Mais c'est une chanteuse française a priori non associée au rock'n roll qui apporte en 1956 une énorme visibilité médiatique au phénomène en formation, Édith Piaf, avec la chanson L'Homme à la moto, indirectement inspirée par L'Équipée sauvage.C'est durant l'été 1959 que l'appellation « blousons noirs » apparaît pour la première fois dans la presse, avec un article de France-Soir du 27 juillet 1959 relatant un affrontement entre bandes survenu au Square Saint-Lambert, dans le XVe arrondissement de Paris[1]. Cette désignation s'impose soudain comme synonyme de « jeunes voyous ». Les journaux se mettent alors à surenchérir en évoquant des bandes caractérisées par leur taille importante (il est question de groupes comptant jusqu'à une centaine de jeunes) et par leur violence. Les « blousons noirs » sont décrits comme des asociaux qui se battent à coups de chaînes de vélo (ou de moto), de coups de poing américains voire de couteaux à cran d'arrêt, qui cherchent la bagarre pour défendre leurs territoires urbains, particulièrement autour des portes de Paris, ou en faisant des descentes dans des bals ou des fêtes.Peu après, les journalistes forgèrent le terme « blousons dorés » pour désigner les jeunes fils de la bourgeoisie qui se faisaient remarquer dans les faits divers, par opposition aux « blousons noirs » qui étaient plutôt issus de milieux populaires.

Cette campagne de presse, qui tourne à la psychose collective, aura pour principal effet de mettre en vogue le genre blouson noir. Autour de 1960, dans tout le pays et dans tous les milieux sociaux, les jeunes gens à la mode aiment à s'habiller de cuir (mais le véritable Perfecto est encore rarissime), portent de grosses chemises à carreaux, se coiffent en arrière avec au sommet du front une large boucle asymétrique souvent brillantinée (la célèbre « banane »). À défaut d'une véritable moto, luxe accessible seulement aux plus fortunés, on roule sur des cyclomoteurs qui en ont à peu près l'aspect, de préférence une Flandria ou une Paloma, une mobylette à la rigueur. La petite délinquance est répandue dans ce milieu, sans être généralisée. Mais afin de choquer, les blousons noirs (qui se nomment eux-mêmes « loulous ») affectent de jouer les durs et de parler des argots empruntés au monde des truands.Ce milieu fournit la base sociale qui sera le marché initial du rock français. Il trouve ses héros en Johnny Hallyday, Eddy Mitchell et spécialement Vince Taylor, avant que la vague yéyé ne relègue au second plan les blousons noirs, à partir de 1963, le tournant a lieu le 22 juin 1963, lors de la « folle nuit de la Nation » : un concert gratuit organisé par Salut les Copains à Paris sur la Place de la Nation attire une immense foule, des incidents graves ont lieu, attribués (à tort ou à raison) à des bandes de blousons noirs. La scène yéyé prend définitivement ses distances avec ces derniers.

Les sociologues qui se penchaient alors sur les origines du problème de la délinquance juvénile évoquaient un conflit de génération ou une révolte contre l'ordre établi, avant d'avancer des facteurs économiques.La thèse la plus courante suggère que les jeunes de tous les pays ayant connu les privations de l'après-guerre se sont lancés à corps perdu dans la recherche de la liberté et le plaisir, voulant jouir immédiatement des biens que la société de consommations leur proposait: musique, moto ou mode. Mais pas assez riche pour pouvoir se les procurer et s'apercevant que la société n'était pas disposée à modifier ses habitudes, ni à ne leur faire aucune concession, ils se révoltèrent et leur enthousiasme se transforma en violence.

D'autres enquêtes au début des années soixante contestent cette thèse en soulignant l'importance de l'urbanisation dans le malaise des jeunes en mettant l'accent sur la concentration de grands ensembles immobiliers dans les villes véritables fabrique de blousons noirs.

"Les cités industrielles sont surtout pathogènes parce qu'elles favorisent les rassemblements de jeunes gens sur un territoire restreint " (109)

Effectivement, les bandes urbaines profilent surtout dans les quartiers abritant des grands immeubles collectifs type HLM ou des groupes d'habitations à bon marché souvent insalubre. Si les blocs HLM marquent un progrès certain par rapport au taudis, l'essentiel y manque trop souvent. La plus part du temps, il n'y a ni jardins, ni espace, ni équipement sportif sans parler de l'absence totale de distraction. Les enfants et les adolescents ont le sentiment d'être en cage et la rue les attire comme un refuge mauvais.

"On ne sait pas quoi faire, racontent des adolescents. Alors on se retrouve et on s'ennuie ensemble "

Parmi les autres facteurs on évoque souvent la carence d'autorité, mais c'est surtout dans la carence du milieu familial qu'il faut rechercher l'origine du drame des blousons noirs ; famille désagrégée, séparations ou divorces, alcoolisme du père.

Pour Henri Joubrel ; la dissociation familiale est la cause essentielle de la conduite asociale d'un nombre grandissant de jeune. Les statistiques montrent que 80 % des jeunes inadaptés sociaux dont on connaît suffisamment l'histoire pour en établir un dossier approfondi sortent d'un foyer dissocié. (111)

Au foyer, ils se sentent mal aimés, les gosses souhaitent la chaleur, ils trouvent le chaos

" Un soir en rentrant chez ma mère elle m'a virée, elle avait un jules " raconte Momo de la bande des Batignolles, après avoir traîné quelques jours dans les rues, le tribunal lui trouvera une famille d'accueil. (112)

" A quatorze ans, je suis parti travailler. Plâtrier. Pourquoi ? Parce que mon père boit et ma mère aussi ". écrit Jean dans Rallye Jeunesse (113)

Ce qui fait dire à un éducateur lyonnais :

" Ce qui déboussole souvent les jeunes, c'est l'impossibilité de prendre leur père pour modèle"

(114)

Si la société cherche les causes du mal dont souffre la jeunesse un autre facteur souvent négligé réside certainement dans le fait qu'ils sont victime de l'incompréhension des adultes. L'emblématique film " La Fureur de Vivre " évoquait déjà ces relations difficiles entre parents et enfant. A la question "mentez--vous à vos parents" posé par un journaliste qui enquête pour un hebdomadaire sur les problèmes de la jeunesse, des jeunes répondent :

" On ne ment pas, on ne parle pas ".

Puis lorsqu'il leur demande : " Que leur reprochez-vous ? ",

ils répondent: " Ils font vraiment une trop sale gueule à table ! " 58 (47)

Dans la même logique , une jeune fille, Raymonde écrit à Rallye Jeunesse

" Ce dont on souffre, c'est de l'ambiance familiale, du manque de vérité, de l'injustice de ce que nous appelons la "vague des croulants" " (116)Dans le conflit adultes jeunes, on assiste même à des faits incroyables comme histoire révélé par l'Humanité ou des jeunes émules des blousons noirs qui pétaradaient la nuit en scooter troublant le sommeil des citoyens de deux patelins ont été tondues par quelques habitants.

" La tête base, le crâne soigneusement tondu, suivant leur chef de fil qui de surcroît avait été dépouillé de son pantalon, plusieurs jeunes gens ont et promené dans les rues de Charly et de Vernaison près de Lyon sous l'œil marqué de la population… " (117)

109 « Les blousons noirs : une société primitive ? » - H.Michel (Directeur du centre de Vaucresson) – J.Selosse (Chargé de recherche au CNRS), In Sciences Avenir N°211, septembre 1964.

110 – « Les blousons noirs : une société primitive ? »

111 – « Mauvais garçons de bonnes familles » Henri Joubrel, Aubier, Editions Montaigne,1959

112 – « Square des Batignoles », Cinq colonnes à la une, 04/11/1960

113 - « Vous avez la parole », in Rallye Jeunesse N°11, février 1960.

114 – « Les garçons sauvage, le blouson noir, une provocateur mais aussi un mal aimé » Le Progrès de Lyon,09/12/1962

115 - "Mauvais garçons de bonnes familles" Henri Joubrel

116 – « Vous avez la parole », in Rallye Jeunesse N°11, février 1960

117 – « Tondeuse pour porteur de blousons », L’humanité, 21 juillet 1961 Si la bande est sociale dans sa structure, elle est par contre anti -sociale par son activité et par sa fonction. Si à l'origine elle ne semble pas se constituer dans un but délinquant, la bande est perçue sous cette forme par la police et la société. En réalité beaucoup de jeunes blousons noirs adoptaient uniquement un mode de comportement sans verser dans la délinquance mais s'exposaient de part ce fait à la réprobation sociale et à la répression. La plupart du temps les actes délictueux ne sont pas prémédités et sont commis dans l'inconscience la plus complète. On cherche surtout à réaliser un coup pour se valoriser sans vraiment se rendre compte de la gravité du délit.

" Ils ne se préoccupent pas exagérément des ennuis qu'ils ont eux avec la justice et ne s'inquiètent pas à l'idée d'avoir un casier judiciaire "(93)

Les Coeurs verts Edouard Luntz (cahiers du cinéma)

Les deux tiers des délits reprochés aux adolescents délinquants sont commis contre la propriété, dont les formes essentielles sont : le vol, les délits visant les deux roues et les actes de vandalisme.

Exemple type de l'activité d'une bande ; celle d'Arpajon dont la police a arrêté le mois de décembre 1959 une vingtaine de membres. Ces garçons âgés de 14 à 18 ans qui suivaient la plupart des cours professionnels dans la région parisienne, se réunissaient chaque jour sur le pont de l'Orge pour y préparer leurs "coups".

" Ils essayaient des blousons en plastique noir et se sauvaient sans les payer. Ils chipaient des disques, pour les écouter ou les revendre. Ils volaient des scooters et des voitures qu'ils abandonnaient hors d'usage. Ils faisaient main basse sur le contenu des autos en stationnement. Ils crevaient les pneus, allumaient des incendies ". (94)

Des adolescents par manque d'argent de poche pratiquent le vol à la tire et certain n'hésitent pas à faire les sacs des veilles dame. Le vol à l'étalage sert des fois pour l'alimentation des surboums. Le vol a parfois l'aspect d'un jeu, d'un défi lancé aux règles sociales.

Les objets volés sont souvent considérés comme des trophées et planqués dans des repaires. C'était le cas pour une bande de Nancy dont les exploits consistaient à voler les objets les plus hétéroclites au cours de cambriolage pour les tenir stockés dans une cave. Le chef de la bande âgé de 16 ans n'a pas hésité à tirer avec une carabine sur les inspecteurs de police venue les arrêter. Ce qui vaudra les assises à trois mineurs. Dans la même région à Charleville, un groupe de six mineurs de 14 et 15 ans connus sous le nom de " La bande des blousons verts " dirigé par un garçon de 20 ans commet 24 vols et cambriolages, le plus souvent la nuit, par effraction. (95)

Dans la région bordelaise chaque membre du gang des As avait son casier dans le garage abandonné qui leur servait de Q.G. on y trouvait les objets les plus hétéroclites, sous-vêtements féminins, couteaux, fer à repasser, boîtes de conserve, appareils photos, jouets, chapelets, rasoirs, statue religieuse etc. Leurs plus beaux trophées; une plaque minéralogique de car de Police Secours qu'ils conservaient jalousement dans leur repaire (96)

Certaines bandes étaient spécialisées dans le casse, lors d'un interrogatoire un jeune raconte avec cynisme ses exploits :

" En pleine nuit, quand nos parents dormaient, on se sauvait et on se retrouvait là... Là, on buvait pour se donner du courage, on s'habillait, on emportait la matraque, et on y allait. On s'habillait tous pareil, avec un masque, pour ne pas être reconnus. Ca commençait par les vitrines des petites veilles. On fait le coup en quelques secondes, à grands coups de matraques. On se donne même pas la peine de voler, ça ne nous intéresse pas... juste une bricole en guise de souvenir. Après le casse on se sauvait en vitesse par des ruelles d'où on n'avait rien pu entendre. On revenait fêter ça et on allait se coucher " (97)

  

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99) Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

La forme la plus significative de la délinquance au tournant de la décennie est sans conteste le vol d'engins motorisés. La possession d'un tel engin est un symbole indéniable de virilité, de prestige (on compare souvent le deux roues au cheval du cow-boy). On l'emprunte pour tomber les filles ou pour s'amuser et s'exalter.

" On fonce la nuit en scooter sur les boulevards de ceinture jusqu'à épuisement de l'essence, le jour on fait peur aux passants sur les trottoirs "

Le plus souvent, après un emprunt à but ludique ou utilitaire, le véhicule est abandonné.

" Son usage répond à un besoin actualisé (retour tardif, fugue, infraction en vue, ou simple promenade le plus souvent) ; le besoin satisfait, le véhicule est abandonné "

" Il s'agit essentiellement de promenade à but ludique ou utilitaire. Ce n'est pas un vol d'appropriation ; sa dangerosité tient surtout au fait que les jeunes commettent des accidents. " (9

Accessoirement, on revend les pièces détachées ou le moteur d'un engin volé est utilisé pour être gonflé afin de faire des courses.

Pour gagner de la puissance sur leurs Flashs ou Flandria à selle bi-place recouverte de simili-cuir en peau de panthère, les lumières d'admission d'échappement sont limées au maximum, la culasse est rabotée. Le carburateur est remplacé, la pipe d'admission est polie intérieurement. Régulièrement lors de ces courses, il y a des accidents avec souvent de grave séquelle pour le conducteur. Un éducateur chargé d'infiltrer une bande à Pessac près de Bordeaux raconte :

" Le départ a lieu à deux kilomètres de là. Cinquante à soixante petits bolides prennent le départ dans un vacarme incroyable, la plupart ont sortit leur pot d'échappement; L'arrivée se fait à une centaine de mètre de la route du Cap- Ferret, mais pratiquement comme ils doivent freiner après la ligne d'arrivée, les engins sur la lancée les amènent à traverser la route en grillant tous les signaux... " (99)

Si longtemps les deux roues jouaient chez nous le rôle de la voiture outre atlantique, le vol de voiture pris rapidement de l'importance avec l'augmentation du parc automobile. Le parc automobile est ainsi passé de moins de 1,5 millions de véhicules en 1950 à 5 millions en 1960. Ces vols étaient facilités par l'absence de clé de contact sur certaine voiture. Comme pour les deux roues, outre le sentiment de puissance la voiture est empruntée pour se griser de vitesse pendant quelques heures, puis abandonnée. A Paris un jeune qui réussi l'exploit de voler une ambulance était considéré à l'unanimité comme le chef de la bande.

 

93 - in "Les blousons noirs, page 114 Centre d'étude de la délinquance juvénile, N°14, Cujas, Bruxelles 1966

94 - "Les vieux , qu'ils crèvent !" in Faim &Soif Février 1960

95 - Maître Jean Hocquet, "Forme nouvelles de la délinquance juvénile" conférence 9 janvier 1960, juripole

96 - "Le gang des As" un Les Gangs d'Adolescents, pages 79,80 op.cit.

97 - Maître Jean Hocquet, op . cit40

98 - J.Sélosse , Vols et voleurs de véhicules à moteur, Cujas 1965

99 - Yves Charrier,Jacques Ellul, Jeunesse délinquante,des blousons noirs aux hippies, page 151, Mercure de France 1971

« LA SOCIETE NOUS AIME PAS, NOUS LES JEUNES ! »

Serge de la bande du Square des Batignolles (Cinq colonnes à la une 1960)

« Ces adolescents effondrés contre les murs, à la manière des cow-boys des westerns le long des cloisons des saloons, sont capables brusquement de lever le cran d'arrêt de leur énergie. Une poussée irrésistible les portes à imiter le Marlo Brando de l'Equipée Sauvage ou le James Dean de la Fureur de vivre"

Henri Joubrel, Jeunesse en danger, Fayard,1960

 

Les blousons noirs sont un phénomène essentiellement urbain. A Paris chaque porte, chaque quartier prolo possède sa bande. Un article de presse daté de l'été 1959 fait état de six bandes principales à Paris et de 70 autres cliques de moindre importance. (76) Selon la préfecture de police 10000 jeunes fréquentent des bandes dans la capitale. (77)

A l'époque la bande la plus importante de la capitale était celle du Talus capable de regrouper 250 à 300 jeunes le samedi soir. Ceux de la porte de St -Ouen se distinguent par la parfaite maîtrise des diverses langues des voyous. La bande du square des Batignolles et leur chef Pilule sont le sujet d'un reportage de l'émission télé Cinq colonnes à la une en 1960. Tout aussi médiatisée, la bande de la Bastille, forte d'une centaine de membres qui parlait un argot forcé. Une enquête est publiée sur eux l'été 1961 par Christian Magret dans le magazine des têtes couronnées Point de Vue. Le chanteur Moustique membre de ce groupe déclare quelques années plus tard dans un entretien:

" A la fin des années 50, on attaquait un car de flics, on cassait les vitres et on piquait le car pour une virée " (7

La bande du Sactos (Sacré Cœur) tournait aussi autour de la centaine et était protégée par leur curé. Elle était très crainte par les autres bandes. Johnny Hallyday qui faisait partie de la bande du square de la Trinité raconte :

«On jouait les durs. On se battait, mais nous fermions notre gueule lorsque la bande du Sacré-Cœur descendait" (79)

La plupart des bandes se singularisaient en arborant le même signe distinctif, qui allait de la manière de se coiffer, aux différents accessoires ; médailles, voir une tête de mort ou un minuscule couteau retenu au cou par une chaîne, bagues, bracelets ou ceinturons incrustés de pièces de monnaie. Cette singularité se retrouve sur leurs engins à deux roues; mobylettes ou scooters : fanions à tête de mort, hélices en plastique de la même couleur gagnées à la fête foraine. La même décalcomanie collée sur le réservoir ou le garde boue ; photos de Tarzan ou de James Dean, vamp, tête d'indien, trèfle à 4 feuilles. L'accessoire peut donner son nom à la bande, ainsi la bande du Damier d'un port breton arborait un damier sur leurs véhicules.

En 1960, 53 % des jeunes qui fréquentaient les bandes sortaient de familles ouvrières, les fils d'employée représentaient 12%.

A noter que 18 % des effectifs des bandes seraient originaires des milieux sociaux supérieurs.

" La majorité de ces jeunes étaient issue des classes sociales défavorisées bien que la bourgeoisie eut ses blousons dorés. Les bandes constituent une configuration culturelle originale, articulée sur une culture de classe. La culture ouvrière en est le soubassement " (80)

Les adolescents de 15 à 17 ans en constituent le noyau le plus important (53, les plus jeunes de 13 à 14 ans représentent 14,8% des membres et ceux de 18 à 20 ans 18,1 % (81) Les blousons noirs des années 1959-1961 appartiennent à la génération des enfants de la guerre, ceux nées pendant la seconde guerre mondiale entre 1939 et 1945 et dans l'immédiate après guerre.

 

Les bandes tournent généralement autour de trois noyaux. Le noyau central composé de ceux qui étaient le plus en vue, quatre à cinq personnes souvent confrontées à la délinquance. Puis vient la bande proprement dite formée en moyenne d'une quinzaine à une vingtaine de membres qui cherchaient surtout à se faire remarquer. Le troisième noyau qui pouvait être plus important jusqu'à une centaine de jeunes était composé des sympathisants et des postulants qui formaient le halo de la bande présent lors des grandes occasions comme une bagarre entre bandes rivales. La bande forme un milieu homogène, l'embryon en est la "cour " où les enfants d'un même immeuble vivent et grandissent ensemble. Vers l'âge de 12 ans les enfants de plusieurs cours se groupent dans des lieux de rencontre plus vaste : places ou squares où ils se forment en bande. Dans la bande, les adolescents se retrouvent et ne s'expriment qu'en symbiose avec les autres.

Le dynamisme du groupe est contenu dans ses motivations qui portent le jeune à avoir en face de lui des interlocuteurs qui le comprennent, qui ont les même besoins et les mêmes soucis que lui et ne par conséquent être des adultes qu'ils haïssent.

" Les vieux ont s 'en fout, ils peuvent tous crever” répond spontanément un jeune blouson noir au juge d'instruction qui lui parlait de ses parents (82).

Pour son reportage dans l'Express, Jean Cau demande à Jojo de la bande de la Porte de Vanves. " Pourquoi "les vieux" à ton avis ne vous comprennent pas ? " réponse de Jojo : " Parce que qu'on voit la vie autrement ! " " Qu'est ce que tu veux dire ? " lui demande alors l'écrivain. Le blond répond à sa place : " Ils voudraient qu'on porte des gilets, qu'on ait des pantalons comme ça, qu'on soit comme eux ! " (83)

Ensemble, ils reconnaissent être différents des autres, mais cette différence, paradoxalement se manifeste par le maximum de conformité avec ceux du groupe. C'est pour cela que le vêtement, la coupe de cheveux, le langage ont une telle importance, ils manifestent une singularité collective. Mais si la panoplie marque la rupture avec le monde adulte, elle ne devait pas être usurpée. Il faut être reconnu par ses pairs, il y a des modèles, l'orgueil, l'honneur et l'exploit ont une grande place dans la vie des bandes. L'intégration dans une bande n'est pas une chose facile. La bande est une société tellement fermée qu'y pénétrer est incontestablement une victoire. Elle passe par deux étapes, celle de la reconnaissance puis celle de l'acceptation. Pour être accepté, il y a des rites d'admissions. Le postulant doit faire ses preuves en réalisant divers exploits qui pouvaient aller du combat au cran d'arrêt à la course de mobylettes dans les sens uniques ou sur les " fortifs " (Certains tronçons des fortifications de 1870 subsistaient encore dans la capitale à la fin des années 50 (84). Parmi les autres exploits couramment pratiqués ; se battre avec le chef ou piquer une nana dans une bande ennemie. Ces pratiques sont souvent associées avec le rituel du " frère de sang " Le chef du gang entaille avec son couteau l'avant bras du postulant, puis fait la même estafilade en forme de croix sur celui du dernier rentré dans le groupe. Il maintient leur deux bras ensemble, unis par le mélange de leur sang, les deux "frères" jurent que jamais ils ne trahiront leurs camarades. Une autre caractéristique de la bande est le vif sentiment de propriété vis à vis de son territoire. Elle a ses lieux de réunion, ses cafés et ses cinémas et n'en change pas et ne tolère pas qu'une autre bande vienne empiéter sa zone, sinon c'est la guerre. Le square, mini espace de verdure apparaît l'endroit idéal pour leurs rassemblements. Là, les garçons discutent ensemble, se racontent des histoires de filles ou de taules souvent exagérées. Ils s'échangent des idées, blaguent, s'amusent, se chamaillent entre eux tout en écoutant de la musique sur un transistor. Dans ce lieu, où ils traînent souvent tard le soir les adolescents éprouvent un sentiment de liberté.La fête foraine est un autre coin qui les attire, et ils aiment se regrouper autour des auto-tamponneuses. Il y règne une certaine ambiance, adossés à la balustrade, ils prennent plaisir à regarder tourner les voitures en écoutant les derniers disques à la mode ou draguer les filles. L'hiver on se met au chaud dans les salles de jeux avec une prédilection pour le flipper. Au Café, ils ne consomment pratiquement pas d'alcool, préférant le diabolo ou le café crème. Paris, connaît l'hiver 1959 la grande vogue du patin à glace. Les patinoires de Saint Didier ou de la " fédé " de Boulogne sont prises d'assaut par des hordes de gamins.

" La fédérale c'est la roue tournante de tous les blousons noirs, on retrouve les copains de tous les quartiers. Il y a des filles, ce n’est pas cher et on s'amuse bien " raconte Pilule chef de la bande des Batignolles (85). Quant au bal, ils y vont très rarement la plupart de ces garçons ne savent pas danser, mais sur place ils aiment bien provoquer des bagarres.

" Le soir d'une fête patronale une quarantaine de jeunes venus de Rouen à scooter, à cyclomoteur ou en taxi, avaient plusieurs fois tenté de pénétrer dans la salle de bal en refusant de payer. L'expulsion par les gendarmes de deux ivrognes leur fournit le prétexte recherché pour passer aux actes de violence. Toute la bande se rua alors sur les représentants de l'ordre et l'un des gendarmes fut roué de coups. Son collègue tira quelques coups en l'air. Ce geste décontenança un temps les agresseurs mais les gendarmes partis, les jeunes gens pénétrèrent en force dans la salle où il brutalisèrent plusieurs danseurs et plusieurs femmes "(86)

Les bandes importantes comportent parfois un tiers de filles. On y trouve souvent des filles garçons qui rêvent d'être des garçons et se conduisent comme tels. Elles revendiquent leur égalité dans les comportements antisociaux et le manifestent notamment par des attitudes de bravades vis à vis de la police lorsque celle-ci intervient. Le journal le Progrès de Lyon raconte le comportement de deux filles membres d'une bande du quartier de Perrache après leur arrestation :

"On reste confondu lorsque l'on sait que ce sont les deux filles qui tinrent tête avec le plus d'aplomb au commissaire et firent preuve d'une inconcevable impolitesse. L'une se contenta de dire : "Je me fous de la police, je me fous de la famille" L'autre, encore plus effronté, n'alla-t-elle pas jusqu'à déclarer : " Parlez moins fort. Vous me faites mal aux oreilles…" (87)Mais la majorité des adolescentes qui fréquentent les bandes peuvent être classées dans la catégorie des "filles-objets" guère respectée qui servent à l'initiation sexuelle des garçons. Elles vont d'un garçon à l'autre, et prennent une sorte de valeur marchande en se faisant échanger pour trois fois rien! Il y aussi les filles attitrées que possèdent les principaux membres de la bande, qui souvent par prudence sont rarement vues par les autres gars. Les filles participent rarement aux délits, mais en sont les complices indirectes en bénéficiant souvent en forme de cadeaux des produits dérobés. Elles aiment se faire conduire dans des véhicules volés, ce qui donne un certain prestige à l'auteur de l'acte délictueux. La délinquance est souvent un moyen de se poser en homme devant la femme pour obtenir ses faveurs. Si quelques séries B américaines de la fin des années cinquante ont fait des gangs de filles l'un de leurs thèmes favoris. L'existence de quelques bandes féminines en France a été confirmée par certains enquêteurs. Lorsque le journal La Montagne évoque une agression commise par une bande de jeunes filles à Caen, on emploie symboliquement le terme de "jupons noirs" : "Les jupons noirs de Caen rouent de coup un Nord-Africain" (8 On note surtout une délinquance féminine opérée en petit groupe dans les grands magasins. Une fille achète un produit pour occuper la vendeuse, une autre fait le guet, tandis que la troisième vole des vêtements ou des aliments. Comme dans l'histoire du film de Marcel Carné " Terrain Vague " on signale des gangs de garçons dirigés par une fille. Exemple, le gang des As une bande délinquante de la région bordelaise qui avait à sa tête Berthe une gamine de 16 ans. (89)

Terrain Vague

Le rapport au travail du blouson noir est complexe. Le gars qui à l'habitude de vivre en bande n'a pas envie de la quitter pour aller bosser, tandis que celui qui travaille de voir ses copains traîner toute la journée lui donne des mauvaises idées et il s'arrête de travailler. Le marché de l'emploi de l'époque le permettant, on travaille selon l'envie ou la nécessité.

" Si le gars travaille, un moment, pendant une semaine ou un ou deux mois, c'est qu'il a besoin d'argent pour s'habiller, pour manger, pour s'acheter une mobylette. Ou bien c'est qu'il s'est produit un renversement moral: son instinct est devenu faible et sa volonté lui a permis de travailler pendant ce temps là " (90)

" Je travaille quand j'ai besoin de fric. S'il me faut une paire de " groles ", je fais la plonge. Si c'est une nécessité plus grave, je me fais embaucher un mois ou deux dans mon métier" . Raconte Guy 18 ans (91)

Les contrats d'apprentissages sont la plupart du temps des contrats pour la forme. Les patrons en profitent pour mal payer les jeunes, mais ils les font travailler comme des ouvriers adultes. En plus, les jeunes apprentis supportent mal les ordres des chefs d'équipes, de ce fait, ils changent régulièrement de métier. Le plus souvent les jeunes des bandes qui travaillent exercent des métiers sans grande qualification comme: télégraphiste, plombier, graisseur. Des métiers où la main d'œuvre est variable qui leur permet de changer de patron, de lieu de travail à leur guise. Lorsqu'on demande à Moustique le benjamin de la bande de la Bastille qui ambitionne de trouver un boulot " pépère " quel genre de travail il aimerait faire, il répond: " Ben : aide routier, livreur en triporteur ou alors être le fils de taulier, avoir une carte de figurant de cinéma ".(92)

 

76 – Philippe Macaigne "Quelques réflexions sur la présentation de la presse écrite des "blousons noirs", in Annales de Vaucresson, N° 2,1964

77 - C.Freinet, « La formation de l’enfance et de la jeunesse », Edition l’école moderne, 1960

78 - Interview Moustique par Christian Victor in Juxe-Box Magazine N° 86, novembre 1994

79 - Interview Johnny Hallyday par Jacques Barsamian in Juke Box Magazine N° 42, novembre 1990

80 - Jean Charles Lagrée in "Les jeunes chantent leurs cultures", page 19,L’Harmattan , 1982

81 - Rapport annuel de l’Education surveillé pour 1960 in "Les bandes d’adolescents","Les classes d'age" page 3 Philippe Robert, Pierre Lascoumes Les éditions ouvrières,Paris 1974

82 - "Les vieux ? qu'ils crèvent ! « Le mal de la jeunesse » ,in Faim & Soif N°33, 7/02/1960

83 - Jean Cau, Les gosses révoltés, l'Express 30 juillet 1959

84 - Long Chris "Johnny", page 17,J'ai Lu N°2380,

85 - "Square des Batignoles" Reportage de Pierre Dumayet, Cinq colonnes à la une,4/11/1960

86 - « Quand la jeunesse faisait peur », Laurent Mucchielli, chercheur au CNRS

87 - "Des blousons noirs sont surpris dans leur repaire par les policier" in Le Progrès de Lyon, 22 mai 1962

88 - La Montagne, 18 juin 1960, Claire Bacher 3Le phénomème bmousons noirs vu par la presse Maitrise faculté de Clermont Ferrant 2000

89 -Philippe Parrot, Monique Gueneau "Le gang des As" in "Les gangs d’adolescents",PUF,1959

90 - in "Cri d'appel d'un blouson noir", page 47, Fayard, 1962

91 - In “tribune libre des jeunes” Cinémonde 16/10/62

92 - in "Les Blousons

 

Blousons noirs. Soixante ans après, l’expression a gardé toute sa force évocatrice, porteuse d’une mythologie cuir mêlant violence et rock’n’roll naissant sur fond de désœuvrement et de misère sociale (ça ne vous rappelle rien ?). Le festival Filmer la musique, que Poptronics suit quotidiennement, y consacre une journée entière avec deux films, une séance de documents d’actualité d’époque et un concert de Magnetix en clôture au Point Ephémère.

1955, « Graine de violence » (« Blackboard Jungle ») sort au cinéma. C’est l’émeute : la jeunesse française découvre en même temps les déhanchements de Presley et le « Rock Around The Clock » de Bill Haley. Les choses ne seront plus tout à fait pareilles : le rock’n’roll vient d’entrer dans la culture populaire hexagonale. Et avec lui, ceux qu’on appelle encore les « tricheurs », d’après le titre du film de Marcel Carné qui sort en 1958, ces jeunes banlieusards des cités qui sortent de terre. Il y a déjà eu quelques gros incidents : à l’été 1955, un concert de Louis Armstrong déclenche une bataille de trois jours dans les rues de Paris, en octobre 1958, le concert de Bill Haley à l’Olympia donne lieu à des débordements : des fauteuils sont détruits par centaines.

  

Mais c’est à l’été 1959 que la France découvre, tétanisée, les blousons noirs. Le 24 juillet, vingt-cinq jeunes de la Porte de Vanves déboulent dans le XVe arrondissement pour affronter la bande du square Saint-Lambert, vêtus de blousons de cuirs, de jeans, et armés de chaînes de vélo. Le lendemain, on se bagarre à Bandol pour une histoire de filles. Quelques jours plus tard, un policier est blessé à Cannes lors d’affrontements avec une bande de Courbevoie. L’affaire fait la Une (« Un agent de police a été sauvagement poignardé par une horde de tricheurs, de blousons noirs »). Les incidents se multiplient tellement (à la sortie de « Jailhouse Rock » en 1960, le cinéma Le Mac Mahon est littéralement pris d’assaut) que le sinistre Maurice Papon, préfet de police de Paris depuis 1958, songe très sérieusement à interdire le rock’n’roll pour préserver la « tranquillité publique ». Cette peur diffuse de la jeunesse, on la retrouve dans les reportages de l’ORTF,

 

Revenir en haut Aller en basDans quel contexte apparaissent les blousons noirs ?

C’est de la délinquance sur fond de rock’n’roll, de guerre d’Algérie et surtout de naissance des cités. A l’époque, face aux barres de Nanterre, La Défense est un immense terrain vague sur lequel seul le Cnit est construit. A peine sortie de terre, cette urbanisation est déjà porteuse de problèmes et provoque désœuvrement, ennui, marginalisation. Il ne fallait pas être visionnaire pour voir que ça allait être le bordel : l’environnement, c’est déjà celui de « Ma 6-t va crack-er ». Cette jeunesse ouvrière qui traîne en bas de ces grandes barres HLM nickel s’emmerde et se radicalise. Les blousons noirs terrorisent les gens, ils niquent toutes les nanas, qui toutes veulent être niquées par eux ! Ils n’ont pas de conscience politique, pas vraiment de conscience sociale non plus, ils sont dans l’énergie brute : ils foutent le bordel et c’est tout.

Quand le mouvement devient-il massif ?

Quand Hallyday débarque, en 1961. C’est un choc. Jusqu’alors, le business de la musique est aux mains de vieux qui se projettent sur les envies des jeunes et suivent les modes. On a affaire à des orchestres de bal qui jouent du twist, quelques mois plus tard ils font du cha-cha ou du calypso. Hallyday, lui, fait de la musique pour les jeunes sans une once de cynisme. Et ça, les kids, ça leur fait péter les plombs. Quand Johnny ou Vince Taylor jouent à l’Olympia au début des années 60, ils cassent tout, ça fait la Une des journaux, avec des slogans choc, ça fait flipper tout le monde car cette expression de la violence des jeunes en groupe est assez nouvelle. Les blousons noirs succèdent en quelque sorte aux apaches du début du siècle, qui eux étaient vraiment dans le banditisme. Là, ce sont des branleurs. C’est assez inédit.

C’est une esthétique aussi...

Oui, les blousons en cuir, les jeans, on est complètement dans le fantasme du motard, de « L’Equipée sauvage ». Brando, avant James Dean, devient une véritable icône de cette jeunesse. Il y a un côté désuet à les revoir aujourd’hui, un mélange de pathétique et de sublime. Le phénomène est assez européen, très présent en Suisse, en Allemagne, mais en France, c’est quelque chose de dur, le cuir, les chaînes, il y a une volonté d’effrayer le bourgeois, de faire peur, un vrai désir de choquer et de provoquer. Aux Etats-Unis, on ne trouve pas tous ces atours, tout cet apparat.

Les blousons noirs disparaissent peu à peu au cours des années 60. C’est la fin du rock’n’roll dans les cités ?

Difficile de dater la fin du mouvement, beaucoup rentrent dans le rang assez vite (selon quelques rares études, plus de la moitié des blousons noirs ont entre 14 et 17 ans, huit sur dix ont moins de vingt ans, ndlr), une petite frange tombe dans la vraie marginalité. Mais le rock ne disparaît pas pour autant du paysage banlieusard. Le rock’n’roll n’a quitté les cités qu’avec l’arrivée du rap. Jusqu’au début des année 80, tout le monde y écoute du rockabilly et du rock’n’roll, qu’on soit blanc, black ou arabe. Gene Vincent est une star des cités. D’ailleurs, ceux qui ont fondé les premiers labels de rap étaient tous d’anciens fans de rockabilly. La naissance des blousons noirs La bande de « Titine » au pied des HLM du Pré-Saint-Gervais. 'agression du jeune Yuriy, en janvier dans le X Ve arrondissement de Paris, a mis en lumière les affrontements entre bandes. Mais à la fin des années 1950 déjà les héritiers des Apaches de la Belle Epoque n’avaient peur de rien ni de personne. Ils aimaient la castagne, les Mobylette et le rock’n’roll. Immersion chez ces petits voyous du Pré-Saint-Gervais, avec le photographe André Lefebvre. La vague est partie des Etats-Unis. Leurs références sont James Dean et sa « Fureur de vivre », Brando dans « L’équipée sauvage ». Partout, ce sont les mêmes jeunes en proie au même mal du siècle. En Angleterre , on les appelle les « Teddy boys », en Allemagne les « Halbstarken », en Suède, les « shunna folke », en France ce sont « les blousons noirs ». L’expression est lancée par le journal « France-Soir », à l’été 1959, après un affrontement entre bandes, square Saint-Lambert, dans le XVe arrondissement de Paris. Avec leurs manteaux de cuir, leurs cheveux mi-longs gominés, leurs chaînes de vélo et leurs poings américains, ils se rassemblent au pied des tours ou des pavillons aux façades décrépies, dans les quartiers populaires des villes ou de leur périphérie. La plupart du temps, les blousons noirs appartiennent à la classe ouvrière, vivent de petits boulots et grandissent dans des familles éclatées. Ils sont les laissés-pour-compte des Trente Glorieuses marquées par l’essor économique et l’émergence de la classe moyenne. Dans le groupe du Pré-Saint-Gervais qu’ont suivi Jean Maquet et André Lefebvre, les journaliste et photographe de Match, la moyenne d’âge est de 16 ans. « Ces jeunes gens sont tout au plus égarés, ils ne sont pas vicieux. Ils vivent en bandes, certes, mais ce mot de bande est trompeur. On pense aux bandes de gangsters, écrit Jean Maquet [...]. Les membres des bandes de blousons noirs, dans l’immense majorité des cas, ne sont que des copains. Il faut insister sur ce point. Il serait on ne peut plus néfaste, et pour tout le monde, que le public se fasse du blouson noir une idée trop noire [...]. Le problème des blousons noirs est grave : il n’est pas encore tragique. » Des copains qui inventent leur propre culture, de nouveaux codes.

Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes @ Sur leurs postes de radio, ils écoutent le rock’n’roll d’Elvis Presley ou de Vince Taylor. Très loin des yéyés. « Ils ont besoin de se sentir virils », écrivait le journaliste de Match. « Cela donne la baston, c’est-à-dire le règlement de comptes à mains nues entre hommes, et, de temps en temps, la “frite”, c’est-à-dire la bagarre générale [...]. Bref, la violence. » Une violence gratuite, pour passer le temps, par exubérance juvénile, par désir de se montrer brave. On se bat pour s’imposer, prendre le pouvoir dans le quartier ou juste pour la gloire, on se tape des virées dans des voitures volées… Ils commettent des larcins, pillent ou cassent plus par défi que par besoin ou conviction. Et, s’ils brandissent leur haine des « flics » et de l’ordre bourgeois, ils ne défendent aucune cause. Leur conscience politique ne ressemble en rien à celle des étudiants de Mai 1968 qui crieront leur révolte quelques années plus tard. Malgré leur rejet de l’autorité, les bandes sont hiérarchisées autour du chef et de ses lieutenants, qui ont tous un surnom. Pour en être, il faut respecter certains rituels, être initié, savoir se montrer téméraire, commettre un vol ou se mesurer à un rival. La presse, qui s’est emparée du phénomène, en fait un mythe. Un congrès sur la délinquance juvénile est même organisé en Italie. Selon les chiffres fournis à l’époque par le ministère de la Justice, en 1959 et 1960, 50 % des jeunes délinquants viennent de ces bandes. Parmi eux, 45 000 ont moins de 18 ans. Comme les loubards ou les jeunes des cités après eux, ils veulent s’affirmer, interroger la société, la provoquer, mettre à l’épreuve sa capacité à les intégrer. En marge, cette jeunesse défavorisée est gangrenée par le désœuvrement. « Sur ce point, ils sont unanimes. Ils s’ennuient, écrivait Jean Maquet. Ils sont incapables de rester seuls. La bande, cette bande fluctuante, c’est ce qui les délivre de leur solitude, leur donne l’illusion d’une fraternité et sans doute, pour beaucoup d’entre eux, d’une famille. Ils ne lui en demandent pas plus. » 69 VENISSIEUX Les MJC 1959-1981 De l'été des blousons noirs à l'été des Minguettes Broché – 3 avril 2008 Les Maisons des jeunes et de la culture (MJC) font partie de ces institutions méconnues bien que souvent évoquées. Parfois confondues avec les Maisons de la culture d'André Malraux, parfois assimilées à de simples maisons de jeunes, elles sont victimes de l'ampleur de leur objectif : lier jeunesse et culture dans une perspective d'éducation populaire. Ce livre retrace leur histoire à leur apogée, entre 1959, lorsque la médiatisation du phénomène blousons noirs favorise une mobilisation en leur faveur, et 1981, quand l'apparition du " mal des banlieues " signalait un changement d'époque : l'insertion sociale des jeunes devenait une priorité tandis que le lien entre jeunesse, loisirs et action culturelle achevait de se dissoudre dans la crise du socio-culturel. Entre ces deux dates, le millier de MJC que comptait alors le territoire a connu une histoire aussi riche que mouvementée. La diversité des activités abritées dans leurs murs n'a d'ailleurs pu que contribuer à rendre les MJC difficilement saisissables : tour à tour foyers de jeunes et maisons pour tous, proposant expérimentations théâtrales et ateliers de bricolage, espaces de débats et sociabilité, elles furent aussi des pépinières pour la formation de militants culturels et politiques locaux. Lieux singuliers qui ont pu être présentés, parfois simultanément, comme des repaires de gauchistes, des centres de propagande communiste et des terreaux de la deuxième gauche, les MJC permettent de saisir la complexité de la vie associative, dans sa richesse mais aussi sa difficulté. Voilà un très beau livre de synthèse sur un sujet qui ne peut manquer d’intéresser les lecteurs de cette revue. Même si les MJC (Maisons des jeunes et de la culture) n’avaient pas pour finalité de contribuer à la lutte contre la délinquance, elles ont été parfois perçues par les municipalités comme un des outils efficaces de prévention, en particulier à l’époque des blousons noirs. Le sous-titre adopté par l’ouvrage rappelle d’ailleurs cet impact possible ou souhaité sur la prévention. Mais Laurent Besse a bien d’autres ambitions ici, et il analyse les MJC à l’aune de l’éducation populaire, et de ses grandes ambitions au lendemain de la Libération. Il les suit donc depuis la République des jeunes, dont l’idée est née au sein du gouvernement de la France libre à Alger (d’après leur fondateur André Philip), jusqu’à l’arrivée de la gauche au pouvoir. En fait, il commence surtout avec leur très forte expansion sous le régime gaulliste avec la nomination de Maurice Herzog, fin 1958, comme haut-commissaire à la Jeunesse et aux Sports. La préface d’Antoine Prost souligne d’ailleurs le paradoxe des MJC : ce sont des institutions de gauche surtout présentes dans les villes de droite et du centre, et Laurent Besse montre que les MJC bénéficient avec Herzog d’un appui essentiel. En 1965, lors de l’anniversaire de leurs vingt ans, la fédération des MJC compte trois fois plus de maisons qu’en 1959. Deux autres paradoxes, soulignés par Antoine Prost, caractérisent les MJC. Elles sont laïques, mais mal vues de la Ligue de l’enseignement. Elles sont destinées aux jeunes, mais accueillent bien d’autres classes d’âge.

2Issu d’une thèse soutenue à Paris-I en 2004, ce livre repose sur une abondante documentation, permettant d’analyser les réactions du tissu local comme les enjeux nationaux, la sociologie des directeurs autant que la philosophie des fondateurs, les pratiques de loisirs autant que les ambitions culturelles. Si les archives de la fédération FFMJC (Fédération française des maisons de jeunes et de la culture), et de la fédération concurrente UNIREG (Union des fédérations régionales de MJC) à partir de 1969, ont été essentielles, elles ont été heureusement complétées par celles des douze principales fédérations régionales, et celles des MJC de quelques grandes villes (Châtellerault, Grenoble, Orléans) ainsi que de fonds privés de militants. L’ouvrage est donc parfaitement étayé, foisonnant de précisions qui en rendent la lecture vivante, et qui n’effacent jamais le souci d’une réflexion synthétique.

3Le livre est bâti sur une chronologie fine, qui distingue trois périodes au cours de ces deux décennies, qui ont vu la multiplication des MJC et leur ouverture à un public élargi. Les 14-21 ans y sont majoritaires dans la décennie 1960 (cf. la première partie « Des maisons pour les jeunes - 1959-1965 »), recrutés parmi les « inorganisés », qui n’appartiennent à aucun mouvement, et dont on souhaite qu’ils viennent aussi bien du monde des ouvriers (les travailleurs manuels), que des étudiants (les lycéens). Le projet des initiateurs des MJC (et l’auteur insiste sur le portrait d’André Philip et de sa philosophie de laïcité ouverte) est d’ouvrir une maison de loisirs culturels et éducatifs pour cette classe d’âge, tous milieux sociaux confondus. Le pari est tenu, en particulier autour des activités de ping-pong et de judo.

4La deuxième partie (« Maisons contestées ? Maisons de la contestation ? 1966-1969 ») insiste sur le choc qu’a été pour la fédération des MJC le départ de Maurice Herzog et son remplacement par François Misoffe, devenu ministre de la Jeunesse et des Sports, hostile aux animateurs et décidé à étouffer ces maisons de la contestation et à les remplacer par « mille clubs » beaucoup plus légers. La fédération est déstabilisée et même si le projet ministériel de suppression de la FFMJC échoue, André Philip démissionne. La FFMJC a fait figure d’administration parallèle et cela ne pouvait pas laisser le pouvoir gaulliste indifférent. C’est le moment aussi où les MJC s’ouvrent aux débats et, sans être le fer de lance de la contestation en 1968, s’en font la caisse de résonance.

5L’interrogation sur « Des maisons pour tous (1970-1971) » qui structure la dernière partie, repose sur le fait que les MJC accueillent alors un public nouveau, de femmes et d’enfants, relativement inconnu jusqu’ici, que l’animateur militant laisse la place peu à peu aux vacataires compétents. Elles deviennent des maisons de loisirs pour tous, et des lieux d’une autre culture, avec multiplication de débats sur les marges et les luttes de tous les peuples. Elles accueillent des chanteurs compositeurs débutants et créent des spectacles appelés à circuler. À la fin des années 1970, la mise en cause du socioculturel est l’enjeu de débats passionnés, et le développement de la crise amorce la réflexion sur l’insertion économique des jeunes autant que sur leur développement culturel. Mais les MJC ne sont pas les seules sur ce terrain…

6Tout au long de l’ouvrage est tenu le fil de la réflexion sur l’éducation populaire, sur ses objectifs, ses contenus, depuis l’ambition des origines, jusqu’aux crises mettant en cause la survie même des MJC, aux prises avec les politiques locales et nationales. Comment développer l’éducation populaire ? Comment intégrer ceux qui refusent la participation régulière aux ateliers, préférant les rencontres informelles du foyer autour du baby-foot ? Comment faire coexister les « intellectuels » avec les autres ? Comment, sans exclure, désamorcer les agressivités, les déprédations ? Le livre aborde l’émergence du métier d’éducateur, qui s’est faite précisément au sein des MJC, dans un milieu qui a longtemps préféré le terme de « directeur » (même en pleine affirmation de la non-directivité des années post 68) à celui d’animateur. Comment les recruter, comment les former ? Il insiste sur le fait que les MJC ont été des équipements discrets, à la différence des maisons de la culture, qui, par comparaison, s’affirmaient dans le paysage urbain comme temples de la culture.

7L’analyse culturelle est étroitement imbriquée dans l’analyse des politiques nationales de la jeunesse, mais aussi des politiques locales. La position originale des MJC qui sont des associations 1901 cogérées avec les municipalités, si elle fournit une initiation à la vie démocratique, est aussi source de conflits avec les municipalités. La place du parti communiste, souvent surestimée, fait des MJC des lieux inquiétants pour les élus de la droite, bien que certains, dans bien des villes, leur soient restés fidèles, sensibles à la qualité de leur travail. La comparaison avec les centres sociaux, beaucoup plus marqués par les militants JOC, en fait ressortir la spécificité essentielle dans une jolie formule. Pour Laurent Besse, le centre social, c’est « l’espace des poussettes », alors que la MJC est « l’espace des mobylettes ».

8La conclusion de Laurent Besse est sévère. Pour lui, l’action des MJC se solde par un relatif échec, dans la mesure où elles n’ont pas été capables de s’adresser en masse aux jeunes. Certes, elles ont été les fruits d’une très grande ambition qui aurait pu faire d’elles, sous la IVe République, ce que les maisons d’école avaient été à la IIIe, et des éducateurs populaires, les nouveaux instituteurs de la République. Certes, elles ont bénéficié de la crise des mouvements d’action catholique. Néanmoins, leur projet de devenir le banc d’essai de la citoyenneté, d’être écoles de la démocratie, n’a pas abouti. L’auteur souligne cependant l’offre qu’elles ont apportée à nombre de petites villes et de villes de banlieue, qui seraient restées des déserts culturels sans elles. Mais leur humanisme polyvalent, qui voulait que l’homme complet soit initié à toutes les disciplines, a cédé devant la spécialisation de la vie associative. En outre à la fin des années 1970, l’heure n’était plus à l’animation, mais à l’insertion professionnelle des jeunes. Et Laurent Besse de conclure sur les difficultés actuelles des MJC, à replacer dans « le contexte de déclin de la ferveur éducative, peut-être de l’utopie éducative ».

Haut de page

Pour citer cet article

Référence papier

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière », 12 | 2010, 256-259.

Référence électronique

Dominique Dessertine, « Laurent Besse, Les MJC, de l'été des blousons noirs à l'été des Minguettes (1959-1981) », Revue d’histoire de l’enfance « irrégulière » [En ligne], 12 | 2010, mis en ligne le 21 juin 2012, consulté le 27 juin 2021. URL : journals.openedition.org/rhei/3212 ; DOI : doi.org/10.4000/rhei.3212

Haut de page

Auteur

Dominique Dessertine

Articles du même auteur

Histoire de l’éducation populaire (1815-1945). Perspectives françaises et internationales [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 22 | 2020

Ces êtres intéressants et infortunés : les enfants trouvés des Basses-Alpes au XIXe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 20 | 2018

Droits des enfants au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 19 | 2017

L’œuvre de secours aux enfants et les populations juives au xxe siècle [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 18 | 2016

Jean-Pierre Méric, Les pionniers de Saint-Sauveur : la colonie agricole du Médoc pour les enfants trouvés (1844-1869) [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 16 | 2014

(Lecture de) Des enfants venus de loin. Histoire de l’adoption internationale en France [Texte intégral]

Paru dans Revue d’histoire de l’enfance « irrégulière », 15 | 2013

Tous les textes...

28 JULY 14

 

I made this mistake of watching the History Channel today, and on it they were discussing what life after an apocalyptic event would really be like for the survivors. It "started" with, there will be dead bodies everywhere which carry with them pathogens, so you'd do best to bury them or burn them as soon as possible to help prevent the spread of disease. Violence will be an immediate danger. In order to protect and defend themselves people will use their guns, knives, axes, whatever to take what's yours if it will help them. The power will be gone, gas and transportation will quickly run out and once workers abandon their posts, the water from your faucet won't be safe to drink and you should switch to bottled water. There is but a thin veneer that holds our society together, the show said, and once people panic, die, are killed in mass numbers, that veneer will completely disappear. People will be desperate including yourselves to get any supplies they can. The show said, we have only to look to Katrina. 2 Days after the storm hit, most stores had been completely looted of every thing from toys to food to tvs. Looters will come, and people will and should form gangs or band together. Security will be the number one thing you will need to have as opposed to going it alone which won't really help you.

 

People will not only steal food, but they will loot houses searching for gold, necessities like clothing, and water, even pets for food---anything they can bargain or trade for with other gangs. If you stay in the city its best to make it look like your house has been sacked by tossing out trash and needless belongings on your lawn and not turning on your lights to attract unwanted persons from the street. Eventually heat, hunger, danger, lack of water, stress, will force you out of the city. A lot of animals will be roaming wild including those from your local zoos. We would also forget that it's not just regular folks out on the street, the prisons will be released into general population. There will be no real law system that can be upheld, and add to that the normal every day sociopaths that you arent' aware of that work with you, live near you, attend your church...without therapy, medications, monitoring, these will also be in the mix. Once you are forced out of the city, survival depends on your ability to be discrete, knowledge of how to survive in the wilderness without cars and everyday necessities, and location of clean water supply and food....

 

...and that's when I stopped watching. I saw the movie, "The Road," and it is the most terrifying and I do believe accurate portrayal of what would happen if disease, nature, or war crippled our society. The history channel show touched on how dumb it is to think that people will still be neighborly and help each other and build this sort of utopian society out of the rubble, and you can do that in perhaps smaller communities away from the big cities, but desperation for food and water are the biggest factors of people turning on one another. When your kids are starving or you are starving, pleasantries, the law, every thing goes out of the window because we all know we will do anything for our own families. It was crazy. I immediately wanted to go and take some survival courses, not that I'm too sure I'd survive the chaos of living in a city which I already hear sirens going off every night and day in!

 

Scary to think. IN other news, Jelly Flops, love them. Jelly Belly sells their bags of the beans that are not the right weight, shape, doubled up, or stuck together at a really cheap price, but they taste obviously the exact same. My favorite flavor has got to be buttered popcorn. It is insane how it just tastes like movie popcorn. It makes me think of Willy Wonka, where they were in the process of creating a 4 course meal in a gum, and Violet Beauregarde snatches up the gum and begins tasting it, and when she gets to the dessert, she swells up like a blueberry b/c Wonka had tried to warn her that the recipe wasn't ready yet. Love that movie. The original that is. I refuse to speak of the Johnny Depp abomination because I fear it will ruin my happy candy loving thoughts of my childhood.

The images (1-3) depict the cell-to-cell translocation of P. gingivalis through host actin fibers after 1 day post-infection in human primary gingival epithelial cells using fluorescence microscopy.

 

This image was chosen as a winner of the 2016 NIH funded research image call.

 

Credit: Dr. Özlem Yilmaz, Dept. of Oral Health Sciences, Medical University of South Carolina

 

This image is not owned by the NIH. It is shared with the public under license. If you have a question about using or reproducing this image, please contact the creator listed in the credits. All rights to the work remain with the original creator.

 

NIH funding from: National Institute of Dental and Craniofacial Research (NIDCR)

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

——————————————————————————

(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

  

-------------------------------------------------- ---------------------

    

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)

_-----------------------------------------

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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)

——————————————————————————

(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

  

-------------------------------------------------- ---------------------

    

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

Sewage Treatment Works, Chelmsford, Essex

Streptococcus pyogenes (Group A Streptococcus) growing on ChromID CPS chromogenic agar. Isolate from a 5 year old male child with urinary tract symptoms and pyrexia

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)

_-----------------------------------------

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

  

-------------------------------------------------- ---------------------

    

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.

———————————————————————————————————————————————— ————

 

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-

 

go.drugbank.com/

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 ...

www.bmj.com

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 ...

www.news-medical.net

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 ...

www.news-medical.net

 

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

 

*********************************************************************

 

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)

_-----------------------------------------

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