CORONA VIRUS OR CORONAVIRUS

The coronavirus ( CoVid-19 ) 

The coronavirus ( CoV ) are viruses that constitute the subfamily Orthocoronavirinae the family Coronaviridae. The name "coronavirus", from the Latin meaning "crown virus", is due to the appearance of virions under an electron microscope, with a fringe of large bulbous projections that resemble the solar corona.

Coronaviruses are equipped with a viral envelope with a genome to RNA positive direction and capsid (hull) kilobases, particularly big for an RNA virus. They rank among the Nidovirals , since all viruses of this order produce a nested set of subgenomic mRNAs during infection. Peak, envelope, membrane, and capsid proteins contribute to the overall structure of all coronaviruses. These RNA viruses are single-stranded and positive in sense (group IV of theBaltimore classification ). They can mutate and recombine .

The bats and birds , as vertebrates flying hot blood , are guests ideal for coronavirus leading the development and spread of coronavirus  . Coronaviruses are normally specific to an animal taxon as host, mammal or bird depending on their species; but these viruses can sometimes change hosts following a mutation. Their human-to-human transmission occurs mainly through close contact via respiratory droplets generated by sneezing and coughing. More than 500 types of coronavirus have been isolated from the bat and there are more than 5,000 types of coronavirus .

Seven main coronaviruses are generally cited as being able to contaminate humans  . An eighth has been identified: B814 (the first human coronavirus identified), but this strain seems to no longer be circulating.

Four circulating coronaviruses are considered harmless : 229E , NL63 , OC43 and HKU1 . They are the cause of 15 to 30% of common colds.

More recently, three types of coronavirus have been identified responsible for serious pneumonitis :

the SARS-CoV , pathogenic agent of Severe Acute Respiratory Syndrome (SARS) 2002-2004

the MERS-CoV , that of Respiratory Syndrome Middle East from 2012

the SARS-CoV-2 , that of disease coronavirus 2019 (Covid-19) appeared in China in 2019 and responsible for a severe pandemic in 2020

Discovery, history

Illustration of the coronavirus morphology. The peplomers, viral spikes club-shaped here colored in red, create the appearance of a ring surrounding the virion, when viewed in the electron microscope.

The coronavirus probably been at least hundreds of millions of years, but from the viewpoint of epidemiology and medical history, and as a zoonosis is the xxi th century they took the importance: five of the seven human coronaviruses have been isolated in this century. And unfortunately, the last three entered our lives with fears related to an epidemic, a pandemic, or death.

It was in 1930 in the United States that the first disease due to a coronavirus was observed in poultry . The following year, a doctor describes in an article the disease which causes respiratory distress in the chicken and a decrease in the laying and the quality of the eggs.

In 1937 the infectious agent, the infectious bronchitis avian virus (IBV for Infectious Bronchitis Virus ) was isolated.

In 1946 , another coronavirus was identified, the porcine gastroenteritis virus (TGE for Transmissible GastroEnteritis ). Independently, in 1949 in New York and 1951 in London , two teams discovered the murine hepatitis virus in a paralyzed mouse.

In 1965 the first coronavirus infecting humans (strain B814 ) was discovered. And quickly, others follow: 229E in 1966 and OC43 in 1967 all of which are the cause of more or less severe colds depending on the person. The following year, they were observed under an electron microscope by June Almeida and David Tyrrell who highlighted their crown structure. A link is made between all these viruses, and the term "coronavirus" was used for the first time in the journal Nature in 1968.

The last human coronavirus (or recently humanized, most probably from one or more strains carried by bats) seems to have emerged in Wuhan in China in 2019: SARS-CoV-2 . The disease it causes ( COVID-19 ) caused in a few months the first major coronavirus pandemic, characterized by a high R0 (2.3 on average according to estimates available in April 2020, but which seems to be able to reach 5 , 7); with a case fatality rate of 6.3 (very variable according to age and context, sometimes exceeding 15%) .

Characterization

The taxonomy of these new viruses is debated first and finally leads in 1975 to the creation of a new family ( Coronaviridae ) and a new subfamily ( Orthocoronavirinae ) by the International Committee on Taxonomy of Viruses .

Naming

The term coronavirus (the Latin corona and viruses , literally "crown virus"  ) comes from the appearance of virions to the electron microscope , characterized by a fringe of large protuberances surrounding the envelope with the appearance of a crown , by analogy with the solar corona .

Virus hosts

The ideal hosts for coronaviruses, as warm-blooded flying vertebrates , are bats (for Alphacoronaviruses and Betacoronaviruses ) and birds (for Gammacoronaviruses (en) and Deltacoronaviruses (en) ) . These reservoir species ensure the evolution and dissemination of coronaviruses . In other species, the symptoms vary (diseases of the upper airway in the chicken, diarrhea in cows or pigs, digestive tracts in cats and dogs, etc.).

Being human is home to four types of naturally mild coronaviruses, which cause infections of the respiratory tract , such as the common cold , and rarely affect the gastrointestinal system , heart and nervous .

Coronavirus groups normally have a specific animal host ( mammals , birds or reptiles  ) but they can sometimes change hosts following a mutation . It is such mutations that have led to the appearance of strains causing serious infections in humans ( SARS, MERS, and Covid-19 ).

Biology

Morphology of a coronavirus.

This enveloped virus consists of a viral envelope surrounding a helical capsid which contains the RNA strand. The genome size of these viruses varies from around 26 to 32 kilobases , values ​​among the highest in RNA viruses .

Coronaviruses have in common proteins designated by a letter indicating their location: S (protuberances), E (envelope), M (membrane) and N (nucleocapsid). Some, in particular those of the A subgroup of the genus Betacoronavirus , have a characteristic HE protein ( hemagglutinin esterase (en) ). The SARS coronavirus further presents on protein S a specific binding site for the angiotensin 2 converting enzyme which serves as an entry point into the host cell .

The physical size of the virion is conventionally given as being 120 to 160 nm or as being of the order of 125 nm . However, SARS-CoV-2 , responsible for Covid-19, has been announced more recently as measuring approximately 60 to 140 nm , and as being elliptical in shape with many variations .

Replication

Replication of the crown virus.

It is done in six successive stages (see illustration):

Thanks to their protein S , coronaviruses bind to surface cell molecules such as metalloproteinases . Viruses endowed with the HE protein (hemagglutinin-esterase) in their envelope can also bind to N-acetylneuraminic acid which acts as co-receptor (itself initiator of the entry of a pathogen in a host cell ). It is unclear whether viruses enter the host cell by fusion of viral and cell membranes, or by receptor internalization . Whatever the mechanism, the RNA strand is inserted into the cell, and the capsid (shell) is abandoned;

Coronaviruses have a single positive-strand RNA genome , which is present in the cytoplasm . The coronavirus RNA genome has a 5 'methylated cap and a 3' polyadenylated tail, which allows RNA to bind to ribosomes for translation. The ribosomes of the cell decode the viral RNA, producing the proteins encoded therein;

First, the virus's positive RNA is transcribed into protein to form its own RNA polymerase (an RNA-dependent RNA polymerase ). Replicase is the first protein produced; once the gene encoding the replicase has been translated by the ribosome of the host cell, translation is stopped by a stop codon. This viral replicase recognizes and produces only viral RNA, and allows the viral genome to be transcribed into new copies of RNA, using the machinery of the host cell. Using the positive strand as a model, this enzyme assembles the negative strand;

Subsequently, this negative-strand itself serves as a model for transcribing small subgenomic RNAs, which are used to make all the other proteins. This is called a nested transcription. This process is a form of genetic economy, allowing the virus to encode the largest number of genes in a small number of nucleotides;

The negative-strand genome is translated by the ribosome of the host cell, and a long polyprotein is formed, where all of the viral proteins are attached. Coronaviruses have a non-structural protein - a protease - which is able to leave the polyprotein.

Furthermore, this negative-strand plays a role in the replication of new positive-strand RNA genomes.

The host cell's cytoplasm fills with protein and

(a) Protein N helps bind genomic RNA to encapsidate the viral genome into a protective envelope called a capsid ; protein M integrates with the membrane of the endoplasmic reticulum , on the capsid side; and proteins HE and S cross the membrane of the endoplasmic reticulum, via the protein of translocation, and are positioned on the opposite side.

(b) With the bond between the capsid and the M proteins, the membrane of the reticulum invaginates, and buds. The assembled capsid (shell) with helical RNA is then found inside the endoplasmic reticulum, having captured the membrane of the latter, which now carries the proteins HE and S outside;

This viral offspring is then (a) encapsulated and transported by golgian vesicles to the cell membrane, (b) to be finally externalized (by exocytosis ) outside the cell.

Coronavirus infection

Types of infection

Seven types of coronavirus commonly infect humans , three of which cause serious infections.

Mild infections

The first four known types are not serious: the human coronaviruses 229E , NL63 , OC43 and HKU1 , unknown in bats. They cause colds with fever and sore throat due to swollen adenoids, mainly in winter and early spring .

Coronaviruses are the cause of 15 to 30% of common colds .

Serious infections

Three types of coronavirus which are not found naturally in humans but in mammals have been discovered more recently and have been the cause of serious infections of the lungs ( viral pneumonia ):

the SARS-CoV, pathogen of the severe acute respiratory syndrome (SARS) which the epidemic from 2002 to 2004 triggered a WHO global alert. It began in China after the consumption in a restaurant of a wild animal, the masked palm civet . The disease killed 774 people (around 10% of those affected). It has been considered eradicated since 2004;

the MERS-CoV , that of the Middle East Respiratory Syndrome , the first outbreak began in Saudi Arabia in 2012. The mortality rate was 35%, making [When?] 449 victims only because of the low number of affected individuals. [ref. necessary] It would have been triggered by the consumption of camel milk and by the proximity to the camels. This disease still exists because to be able to eradicate it, it would be necessary that the populations which use traditionally camels can do without it;

the SARS-CoV-2 , that of disease coronavirus 2019 (Covid-19) appeared in China in 2019 and responsible for a severe pandemic in 2020 . The consumption of pangolin meat and bats (sold for food in China) could be at the origin.

Depending on the virus involved, severe forms of the disease have their peculiarities. For example, diarrhea was very common in SARS but rare in 2019 coronavirus disease .

Comparison of serious infections

Three main sources are used: the Institut Pasteur , the WHO and the American CDC  .

Middle East Respiratory Syndrome (MERS),  Severe acute respiratory syndrome (SARS), Coronavirus disease 2019 (COVID-19)

agent pathogenic MERS-CoV SARS-CoV SARS-CoV-2

Year of appearance 2012 2003 2019

Number of cases 1,219 8,098 including 5,327 in China. In progress, see here

Percentage of cases by nosocomial transmission 70% [ 29 ] 58%

Number of deaths 449 774 (including 349 in China) In progress, see here

Tank Camel Bat Bat (probably)

Transmission to humans by animals Direct contact with an infected animal, consumption of raw dromedary milk . Consumption of masked palm civet meat , wild animal sold on markets and consumed in southern China. Pangolin is said to be the intermediate host.

Human-to-human transmission Yes Yes Yes

Transmission by object - Yes Very low risk.

Maternal-fetal transmission - No case has been found in pregnant women infected with this virus . No evidence.

Transmission through breast milk Only one documented case RT-PCR negative on 16 women tested

Incubation Between 5 and 15 days. Between 2 and 7 days. Median incubation time at 5.1 days (5.5 days on average), 97.5% of people will be sick 11.5 days after infectious contact .

Healthy carrier - Probably not. Yes , (only one case published)

Contagiousness Reproduction rate less than 1 . Reproduction rate greater than 2. Median of the basic reproduction rate (R 0 ) at 2.79 .

Duration of contagiousness - - Seems limited to the period of clinical signs. Contested possibility of contagion in asymptomatic phase.

Beginning of the infectious period - 3 to 4 days after the onset of clinical signs. From the appearance of clinical signs. Proven asymptomatic carrier.

Fever 98% 99% At 87.9%, but can appear several days after coughing or difficulty breathing.

Diarrhea At 26% At 20% . At 3.7%.

Stool transmission Very likely but played a minor role. This possibility is envisaged .

Lethality 34.4% 9.5%  , beyond 50% in those over 65 years of age. 3.4%

Treatment Symptomatic Symptomatic Symptomatic

Vaccine No No No

Status Possible resurgence. Considered eradicated. Ongoing epidemic .

Passing the cash barrier

In view of the available genomic sequences, two major animal taxa would be the main reservoir for CoVs:

bats : natural hosts of HCoV-NL63 and HCoV-229E  ;

rodents : natural hosts of HCoV-OC43 and HKU1.

In view of the available knowledge, the coronaviruses seemed to need intermediate hosts (always mammals) to "humanize", that is to say to mutate in order to infect humans.

Known intermediate hosts have been:

of cattle for HCoV-OC43 ;

the alpaca for HCoV-229E  ;

the civet hidden for SARS-CoV  ;

the dromedary for the MERS-CoV .

Human-to-human transmission

For the 2019-2020 pandemic, see the articles whose names follow.

Current pandemic and country reactions with figures in all countries: Covid-19 pandemic .

Pandemic in France: Covid-19 pandemic in France .

For transmission, incubation, contagiousness, signs and others: Coronavirus disease 2019 .

For the virus responsible for the disease: Coronavirus 2 of severe acute respiratory syndrome .

Particles ejected by a sneeze.

Human-to-human transmission of coronaviruses is primarily through respiratory droplets or aerosols expectorated by an infected person (via coughing, sneezing, postillions, or sometimes just by speaking loudly or shouting ) when the virus particles are inhaled by a person is nearby. Transmission and contagiousness also vary according to the coronavirus, and perhaps according to its strain within an epidemic.

The prophylaxis requires a primary prevention to limit transmission of the virus: avoid contact (potentially contaminated surfaces, handshakes, hugs), wash hands frequently, avoid touching your eyes, nose or mouth, where the virus can enter the body. If you have cough or cold symptoms, keep at least 1 meter from anyone and avoid emitting contaminated particles.

Other recommendations include:

do not come into contact with obviously sick animals, do not consume meat from sick animals;

do not consume undercooked animal products (meat, etc.), or raw vegetables if they have not been washed with uncontaminated water.

Treatment

In the case of SARS, drugs have been used to try to stem the epidemic: ribavirin , a nucleotide analogue, steroidal anti-inflammatory drugs and, after formal identification of the pathogen and sensitivity screens, ' interferon-alpha and protease inhibitors . Their effectiveness is still questionable. None has been the subject of an adequate clinical study: many available studies do not allow clear scientific conclusions because they were carried out on small numbers of subjects or without protocol or fixed dose. Some even indicate that these treatments could have harmed the eradicationf the previous SARS epidemic has not given way to many clinical trials. Of vaccines based on inactivated virus, and others based on the S and N proteins, are under study for several years .

Taxonomy

Naming of coronaviruses

Coronaviruses are appointed by a study group working within the International Committee on Taxonomy of Viruses (ICTV ).

Classification

The coronavirus ( CoV ) are RNA viruses single strand of sense positive (group IV of the Baltimore classification ) corresponding to the subfamily Orthocoronavirinae the taxonomy of ICTV , in the family of Coronaviridae , order of Nidovirales and the kingdom of Riboviria.

Four genera contain viruses that are pathogenic for mammals:

Alphacoronavirus , which includes the porcine epidemic diarrhea virus (PEDV) virus transmissible gastroenteritis (TGEV), coronavirus swine acute diarrhea syndrome (SADS-CoV), the coronavirus canine enteric The enteric coronavirus feline , feline infectious peritonitis virus (FIPV);

Betacoronavirus , including respiratory-respiratory SARS virus ( SARS-CoV ), SARS-CoV-2 , Middle East respiratory syndrome coronavirus ( MERS-CoV ), murine hepatitis virus ( MHV ), bovine coronavirus , rat sialodacryoadenitis virus, porcine sialodacryoadenitis virus, porcine hemagglutinosis, porcine hemagglutinosis virus equine coronavirus. In this genus Betacoronavirus, SARS-CoV and SARS-CoV-2 both belong to the subgenus Sarbecovirus in which three distinct clades have been identified:

Clade1 : batSARSr-CoVstrainsdeBulgariaandKenya ;

Clade2 : SARS-CoV-2etbatSARSr-CoVstrainsfreasteasteastChina ;

Clade3 : SARS-CoVandbatSARSr-CoVstrainsfromsouthwesternChina:

Gammacoronavirus : mainly found in migratory birds, causing in particular bronchitis; a Gammacoronavirus has been isolated from a captive beluga ,

Deltacoronavirus : recently known, which seem to mainly infect birds, but also found in pigs.

Notes: A coronavirus is sometimes called according to the animal species where it was found (for example: canine respiratory coronavirus, or CRCoV for Canine respiratory coronavirus , virus belonging to the genus betacoronavirus and its subgroup 2a) .

The last pandemic coronavirus found in 2020 is SARS-CoV-2 .

Four genera contain viruses that are pathogenic for mammals:

Alphacoronavirus , which includes the porcine epidemic diarrhea virus (PEDV) virus transmissible gastroenteritis (TGEV), coronavirus swine acute diarrhea syndrome (SADS-CoV), the coronavirus canine enteric The enteric coronavirus feline , feline infectious peritonitis virus (FIPV);

Betacoronavirus , including respiratory-respiratory SARS virus ( SARS-CoV ), SARS-CoV-2 , Middle East respiratory syndrome coronavirus ( MERS-CoV ), murine hepatitis virus ( MHV ), bovine coronavirus , rat sialodacryoadenitis virus, porcine sialodacryoadenitis virus, porcine hemagglutinins, porcine hemagglutinin virus equine coronavirus. In this genus Betacoronavirus, SARS-CoV and SARS-CoV-2 both belong to the subgenus Sarbecovirus in which three distinct clades have been identified:

Clade1 : batSARSr-CoVstrainsdeBulgariaandKenya ;

Clade2 : SARS-CoV-2etbatSARSr-CoVstrainsfreasteasteastChina ;

Clade3 : SARS-CoVandbatSARSr-CoVstrainsfromsouthwesternChina:

Gammacoronavirus: mainly found in migratory birds, causing in particular bronchitis; a Gammacoronavirus has been isolated from a captive beluga,

Deltacoronavirus : recently known, which seem to mainly infect birds, but also found in pigs.

Notes: A coronavirus is sometimes called according to the animal species where it was found (for example: canine respiratory coronavirus, or CRCoV for Canine respiratory coronavirus , virus belonging to the genus betacoronavirus and its subgroup 2a).

The last pandemic coronavirus found in 2020 is SARS-CoV-2 .

List of species

The Orthocoronavirinae subfamily of the Coronaviridae family is organized into 4 genera, 22 subgenera and around 40 species :

Subfamily Orthocoronavirinae

Genus Alphacoronavirus

Subgenus Colacovirus

Bat coronavirus CDPHE15

Subgenus Decacovirus

Bat coronavirus HKU10

Rhinolophus ferrumequinum alphacoronavirus HuB-2013

Subgenus Duvinacovirus

Human coronavirus 229E (HCoV-229E)

Luchacovirus subgenus

Lucheng Rn rat coronavirus

Subgenus Minacovirus

Ferret coronavirus

Mink coronavirus 1

Subgenus Minunacovirus

Miniopterus bat coronavirus 1

Miniopterus bat coronavirus HKU8

Myotacovirus Subgenus

Myotis rickety alphacoronavirus Sax-2011

Nyctacovirus

Nyctalus velutinus alphacoronavirus SC-2013

Subgenus Pedacovirus

Porcine epidemic diarrhea virus

Scotophilus bat coronavirus 512

Subgenus Rhinacovirus

Rhinolophus bat coronavirus HKU2

Subgenus Setracovirus

Human coronavirus NL63 (HCoV-NL63)

NL63-related bat coronavirus strain BtKYNL63-9b

Subgenus Tegacovirus

Alphacoronavirus 1

Genus Betacoronavirus

Subgenus Embecovirus

Betacoronavirus 1 (incl. Human coronavirus OC43 , HCoV-OC43)

China Rattus coronavirus HKU24

Human coronavirus HKU1 (HCoV-HKU1)

Murine coronavirus

Subgenus Hibecovirus

Bat Hp-betacoronavirus Zhejiang2013

Subgenus Merbecovirus

Hedgehog coronavirus 1

Middle East respiratory syndrome-related coronavirus (MERS-CoV)

Pipistrellus bat coronavirus HKU5

Tylonycteris bat coronavirus HKU4

Subgenus Nobecovirus

Rousettus bat coronavirus GCCDC1

Rousettus bat coronavirus HKU9

Subgenus Sarbecovirus

Severe acute respiratory syndrome-related coronavirus (SARS-CoV)

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2)

Genus Gammacoronavirus

Subgenus Cegacovirus

Beluga whale coronavirus SW1

Subgenus Igacovirus

Avian infectious bronchitis coronavirus

Kind Deltacoronavirus

Subgenus Andecovirus

Wigeon coronavirus HKU20

Buldecovirus Subgenus

Bulbul coronavirus HKU11

HKU15 Coronavirus

Munia coronavirus HKU13

White-eye coronavirus HKU16

Herdecovirus Subgenus

Night heron coronavirus HKU19

Moordecovirus Subgenus

Common moorhen coronavirus HKU21

Source: Wikipedia.com