Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused byinfectious bronchitis virus(IBV).Arthur Schalk and MC Hawn described in 1931 a newrespiratory infection of chickensinNorth Dakota. The infection of new-born chicks was characterized by gasping and listlessness. The mortality rate of the chicks was 40–90%.In 1937, Fred Beaudette and Charles Hudson reported that they had successfully isolated and cultivated the infectious bronchitis virus which caused the disease.In the 1940s, two more animal coronaviruses,mouse hepatitis virus(MHV) andtransmissible gastroenteritis virus(TGEV), were isolated.It was not realized at the time that these three different viruses were related.
The name “coronavirus” is derived from Latincorona, meaning “crown” or “wreath”, itself a borrowing fromGreekκορώνηkorṓnē, “garland, wreath”.The name was first used in 1968 by an informal group of virologists in the journalNatureto designate the new family of viruses. The name refers to the characteristic appearance ofvirions(the infective form of the virus) byelectron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of asolar corona. Thismorphologyis created by the viral spikepeplomers, which areproteinson the surface of the virus.
Coronaviruses are largepleomorphicspherical particles with bulbous surface projections.The average diameter of the virus particles is around 120nm(.12μm). The diameter of the envelope is ~80 nm (.08 μm) and thespikesare ~20 nm (.02 μm) long. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells.
Inside the envelope, there is thenucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-strandedRNAgenome in a continuousbeads-on-a-stringtype conformation.The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.
The genome organization for a coronavirus is5′-leader-UTR-replicase/transcriptase-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3′UTR-poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase/transcriptase polyprotein. The replicase/transcriptase polyprotein self cleaves to formnonstructural proteins.
The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid.Interspersed between these reading frames are the reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus.
Infection begins when the viral spike (S) glycoprotein attaches to its complementary host cell receptor. After attachment, aproteaseof the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows thevirus to enterthe host cell byendocytosisor direct fusion of the viral envelop with thehost membrane.
A number of the nonstructural proteins coalesce to form amulti-proteinreplicase-transcriptase complex (RTC). The main replicase-transcriptase protein is theRNA-dependent RNA polymerase(RdRp). It is directly involved in thereplicationandtranscriptionof RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. Theexoribonucleasenonstructural protein, for instance, provides extra fidelity to replication by providing aproofreadingfunction which the RNA-dependent RNA polymerase lacks.
One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates thesynthesisof negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.The other important function of the complex is to transcribe the viral genome. RdRp directly mediates thesynthesisof negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sensemRNAs.
The replicated positive-sense genomic RNA becomes the genome of theprogeny viruses. The mRNAs are gene transcripts of the last third of the virus genome after the initial overlapping reading frame. These mRNAs are translated by the host’s ribosomes into the structural proteins and a number of accessory proteins.RNA translation occurs inside theendoplasmic reticulum. The viral structural proteins S, E, and M move along the secretory pathway into theGolgi intermediate compartment. There, the M proteins direct most protein-protein interactions required for assembly of viruses following its binding to thenucleocapsid.Progeny viruses are then released from the host cell byexocytosisthrough secretory vesicles.
The scientific name for coronavirus isOrthocoronavirinaeorCoronavirinae.Coronaviruses belong to the family ofCoronaviridae,orderNidovirales,and realmRiboviria.They are divided into alphacoronaviruses and betacoronaviruses which infect mammals – and gammacoronaviruses and deltacoronaviruses which primarily infect birds.
Themost recent common ancestor(MRCA) of all coronaviruses is estimated to have existed as recently as 8000BCE, although some models place the common ancestor as far back as 55 million years or more, implying long term coevolution with bat and avian species.The most recent common ancestor of the alphacoronavirus line has been placed at about 2400 BCE, the betacoronavirus line at 3300 BCE, the gammacoronavirus line at 2800 BCE, and the deltacoronavirus line at about 3000 BCE. Bats and birds, aswarm-bloodedflying vertebrates, are an idealnatural reservoirfor the coronavirus gene pool (bats the reservoirfor alphacoronavirus and betacoronavirus – and birds the reservoir for gammacoronavirus and deltacoronavirus). The large number of host bat and avian species, and their global range, has enabled extensive evolution and dissemination of coronaviruses.
Many human coronavirus have their origin in bats.The human coronavirus NL63 shared a common ancestor with a bat coronavirus (ARCoV.2) between 1190–1449 CE.The human coronavirus 229E shared a common ancestor with bat coronavirus (GhanaGrp1 Bt CoV) between 1686–1800 CE.More recently,alpacacoronavirus and human coronavirus 229E diverged sometime before 1960.MERS-CoV emerged in humans from bats through the intermediate host of camels.MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.The most closely related bat coronavirus and SARS-CoV diverged in 1986.A possible path of evolution, of SARS coronavirus and keen bat coronaviruses, suggests that SARS related coronaviruses coevolved in bats for a long time. The ancestors of SARS-CoV first infected leaf-nose bats of the genusHipposideridae;subsequently, they spread to horseshoe bats in the speciesRhinolophidae,and then tocivets, and finally to humans.
Unlike other betacoronaviruses,bovine coronavirusof the speciesBetacoronavirus 1and subgenusEmbecovirusis thought to have originated inrodentsand not in bats.In the 1790s, equine coronavirus diverged from the bovine coronavirus after across-species jump.Later in the 1890s, human coronavirus OC43 diverged from bovine coronavirus after another cross-species spillover event.It is speculated that theflu pandemic of 1890may have been caused by this spillover event, and not by theinfluenza virus, because of the related timing, neurological symptoms, and unknown causative agent of the pandemic.Human coronavirus OC43 besides causing respiratory infections is also suspected of playing a role inneurological diseases.In the 1950s, the human coronavirus OC43 began to diverge into its presentgenotypes.Phylogentically, mouse hepatitis virus (Murine coronavirus), which infects the mouse’s liver and thecentral nervous system,is related to human coronavirus OC43 and bovine coronavirus. Human coronavirus HKU1, like the aforementioned viruses, also has its origins in rodents.
Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether. Four of these coronaviruses continually circulate in the human population and produce the generally mild symptoms of thecommon coldin adults and children worldwide: -OC43, -HKU1, HCoV-229E, -NL63.Coronaviruses cause about 15% of commons colds.The majority of colds are caused byrhinoviruses.The four mild coronaviruses have a seasonal incidence occurring in the winter months intemperate climates.There is no preference towards a particular season intropical climates.
Four human coronaviruses produce symptoms that are generally mild:
In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, theWorld Health Organization(WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people were infected, about ten percent of whom died.
Middle East respiratory syndrome (MERS)
In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV).The World Health Organization issued a global alert soon after.The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person.However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health.In addition, cases of human-to-human transmission were reported by the Ministry of Health inTunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus.By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.
After the DutchErasmus Medical Centresequenced the virus, the virus was given a new name, Human Coronavirus—Erasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014.
In May 2015, an outbreak of MERS-CoV occurred in theRepublic of Korea, when a man who had traveled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East.As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%.
As of20 April 2020, there have been at least165,939confirmed deaths and more than2,416,135confirmed cases in thecoronavirus pneumonia pandemic. The Wuhan strain has been identified as a new strain ofBetacoronavirusfrom group 2B with approximately 70% genetic similarity to the SARS-CoV.The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well.The pandemic has resulted in travel restrictions and nationwide lockdowns in several countries.
Coronaviruses primarily infect theupper respiratoryandgastrointestinal tractof mammals and birds. They also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. In chickens, theinfectious bronchitis virus(IBV), a coronavirus, targets not only the respiratory tract but also theurogenital tract. The virus can spread to different organs throughout the chicken.Economically significant coronaviruses of farm animals includeporcinecoronavirus (transmissible gastroenteritis coronavirus, TGE) andbovine coronavirus, which both result indiarrheain young animals.Feline coronavirus: two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneousmutationof this virus can result infeline infectious peritonitis(FIP), a disease associated with high mortality. Similarly, there are two types of coronavirus that infect ferrets: Ferret enteric coronavirus causes a gastrointestinal syndrome known as epizootic catarrhal enteritis (ECE), and a more lethal systemic version of the virus (like FIP in cats) known as ferret systemic coronavirus (FSC).There are two types ofcanine coronavirus(CCoV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease.Mouse hepatitis virus(MHV) is a coronavirus that causes an epidemicmurineillness with high mortality, especially among colonies of laboratory mice.Sialodacryoadenitis virus (SDAV) is highly infectious coronavirus of laboratory rats, which can be transmitted between individuals by direct contact and indirectly by aerosol. Acute infections have highmorbidityandtropismfor the salivary, lachrymal andharderian glands.
Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus bothin vivoandin vitroas well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model formultiple sclerosis. Significant research efforts have been focused on elucidating theviral pathogenesisof these animal coronaviruses, especially byvirologistsinterested in veterinary andzoonoticdiseases.