Coronavirus

For the ongoing outbreak, see 2019–20 Wuhan coronavirus outbreak. For the specific virus causing this outbreak, see Novel coronavirus (2019-nCoV).

Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, the viruses cause respiratory infections – including the common
cold – which are typically mild. Rarer forms such as SARS, MERS and the novel coronavirus causing the 2019–20 Wuhan coronavirus outbreak can be lethal. In cows and pigs coronaviruses cause diarrhea. In chickens they cause an upper respiratory disease. There are no vaccines or antiviral drugs that are approved for prevention or treatment.

Coronaviruses are viruses in the subfamily Orthocoronavirinae in the family Coronaviridae, in the order Nidovirales.[4][5] Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and with a nucleocapsid of helical symmetry. The genomic size of coronaviruses ranges from approximately 26 to 32 kilobases, the largest for an RNA virus.

The name “coronavirus” is derived from the Latin corona, meaning crown or halo, which refers to the characteristic appearance of the virus particles (virions): they have a fringe reminiscent of a royal crown or of the solar corona.

Discovery

Coronaviruses were discovered in the 1960s.[6] The earliest ones discovered were infectious bronchitis virus in chickens and two viruses from the nasal cavities of human patients with the common cold that were subsequently named human coronavirus 229E and human coronavirus OC43.[7] Other members of this family have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and 2019-nCoV in 2019; most of these have been involved in serious respiratory tract infections.

Name and morphology

The name “coronavirus” is derived from the Latin corona and the Greek κορώνη (korṓnē, “garland, wreath”), meaning crown or halo. This refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of a royal crown or of the solar corona. This morphology is created by the viral spike (S) peplomers, which are proteins that populate the surface of the virus and determine host tropism.

Proteins that contribute to the overall structure of all coronaviruses are the spike (S), envelope (E), membrane (M), and nucleocapsid (N). In the specific case of the SARS coronavirus (see below), a defined receptor-binding domain on S mediates the attachment of the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[8] Some coronaviruses (specifically the members of Betacoronavirus subgroup A) also have a shorter spike-like protein called hemagglutinin esterase (HE).[4]

Replication

Following the entry of this virus into the cell, the virus particle is uncoated and the RNA genome is deposited into the cytoplasm.

The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail. This allows the RNA to attach to ribosomes for translation.

Coronaviruses also have a protein known as a replicase encoded in its genome which allows the RNA viral genome to be transcribed into new RNA copies using the host cell’s machinery. The replicase is the first protein to be made; once the gene encoding the replicase is translated, the translation is stopped by a stop codon. This is known as a nested transcript. When the mRNA transcript only encodes one gene, it is monocistronic. A coronavirus non-structural protein provides extra fidelity to replication because it confers a proofreading function,[9] which is lacking in RNA-dependent RNA polymerase enzymes alone.

The RNA genome is replicated and a long polyprotein is formed, where all of the proteins are attached. Coronaviruses have a non-structural protein – a protease – which is able to separate the proteins in the chain. This is a form of genetic economy for the virus, allowing it to encode the greatest number of genes in a small number of nucleotides.[10]

Transmission

Human to human transmission of coronaviruses is primarily thought to occur among close contacts via respiratory droplets generated by sneezing and coughing

Taxonomy

Genus: Alphacoronavirus; type species: Alphacoronavirus 1[12][13]
Species: Alpaca coronavirus, Alphacoronavirus 1, Human coronavirus 229E, Human Coronavirus NL63, Miniopterus Bat coronavirus 1, Miniopterus Bat coronavirus HKU8, Porcine epidemic diarrhea virus, Rhinolophus Bat coronavirus HKU2, Scotophilus Bat coronavirus 512
Genus Betacoronavirus; type species: Murine coronavirus
Species: Betacoronavirus 1, Human coronavirus HKU1, Murine coronavirus, Pipistrellus Bat coronavirus HKU5, Rousettus Bat coronavirus HKU9, SARS coronavirus, Tylonycteris Bat coronavirus HKU4, MERS-CoV, Human coronavirus OC43, Hedgehog coronavirus 1 (EriCoV), 2019-nCoV
Genus Deltacoronavirus; type species: Bulbul coronavirus HKU11
Species: Wigeon coronavirus HKU20, Bulbul coronavirus HKU11, Porcine coronavirus HKU15, Munia coronavirus HKU13, Thrush coronavirus HKU12
Genus Gammacoronavirus; type species: Infectious bronchitis virus
Species: Beluga whale coronavirus SW1, Infectious bronchitis virus

Evolution

The most recent common ancestor of the coronavirus has been placed at 8000 BCE.[14] They may be considerably older than this. Another estimate places the most recent common ancestor (MRCA) of all coronaviruses around 8100 BCE. The MRCA of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus have been placed at about 2400 BCE, 3300 BCE, 2800 BCE and 3000 BCE, respectively. It appears that bats and birds, the warm-blooded flying vertebrates, are ideal hosts for the coronavirus gene source (with bats for Alphacoronavirus and Betacoronavirus, and birds for Gammacoronavirus and Deltacoronavirus) to fuel coronavirus evolution and dissemination.[15]

Bovine coronavirus and canine respiratory coronavirus diverged from a common ancestor in 1951.[16] Bovine coronavirus and human coronavirus OC43 diverged in 1899. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century. Another estimate suggests that human coronavirus OC43 diverged from bovine coronavirus in 1890.[17]

The MRCA of human coronavirus OC43 has been dated to the 1950s.[18]

Middle East respiratory syndrome coronavirus, although related to several bat species, appears to have diverged from these several centuries ago.[19] The human coronavirus NL63 and a bat coronavirus shared an MRCA 563–822 years ago.[20]

The most closely related bat coronavirus and the SARS coronavirus diverged in 1986.[21] A path of evolution of the SARS virus and keen relationship with bats have been proposed.[22][23] The authors suggest that the coronaviruses have been coevolved with bats for a long time and the ancestors of SARS virus first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets, and finally to humans.[citation needed]

Alpaca coronavirus and human coronavirus 229E diverged before 1960.[24]

Human coronaviruses

Coronaviruses are believed to cause a significant percentage of all common colds in human adults and children. Coronaviruses cause colds with major symptoms, e.g. fever, throat swollen adenoids, in humans primarily in the winter and early spring seasons.[25] Coronaviruses can cause pneumonia, either direct viral pneumonia or a secondary bacterial pneumonia and they can also cause bronchitis, either direct viral bronchitis or a secondary bacterial bronchitis.[26] The much publicized human coronavirus discovered in 2003, SARS-CoV which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections.[26]

There are seven strains of human coronaviruses:

Human coronavirus 229E (HCoV-229E)
Human coronavirus OC43 (HCoV-OC43)
Severe acute respiratory syndrome-related coronavirus (SARS-CoV)
Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
Human coronavirus HKU1
Middle East respiratory syndrome-related coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC.
Novel coronavirus (2019-nCoV),[27][28] also known as Wuhan coronavirus.[29] (‘Novel’ in this case means newly discovered, or newly originated, and is a placeholder name.)[28]
The coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and children world-wide.[30]

Novel coronavirus (2019-nCoV)

Main article: Novel coronavirus (2019-nCoV)

In December 2019, a pneumonia outbreak was reported in Wuhan, China.[42] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[43] which was labeled as 2019-nCoV by the World Health Organization (WHO).[27][28][44]

As of 3 February 2020 (10:33 UTC), there have been 427 confirmed deaths and more than 20,600 confirmed cases in the coronavirus pneumonia outbreak.[45][46] The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with an ~70% genetic similarity to the SARS-CoV.[47] The virus was suspected to have originated in snakes,[48] but many leading researchers disagree with this conclusion.[49] The virus has a 96% percent similarity to a bat coronavirus, so an origin in bats is widely suspected.[50][51]

Other animals

Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the early 1970s. Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.[52]

Diseases caused

Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of 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, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the urogenital tract. The virus can spread to different organs throughout the chicken.[53] Economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline coronavirus: two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline 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 in ferrets as ferret systemic coronavirus (FSC).[54] There are two types of canine 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 epidemic murine illness with high mortality, especially among colonies of laboratory mice.[55] 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 high morbidity and tropism for the salivary, lachrymal and harderian glands.[56]

A HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.[57]

Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as 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 for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.[58]