Coronavirus

Orthocoronavirinae
Coronaviruses 004 lores.jpg
Electron micrograph of infectious bronchitis virus virions
2019-nCoV-CDC-23312 without background.png
Render of 2019-nCoV virion
Virus classification e
(unranked): Virus
Realm: Riboviria
Phylum: incertae sedis
Order: Nidovirales
Family: Coronaviridae
Subfamily: Orthocoronavirinae
Genera[1]
Synonyms[2][3]
  • Coronavirinae

A coronavirus is one of a number of viruses that cause diseases in mammals and birds. In humans, the viruses cause respiratory infections, including the common cold, which are typically mild, though rarer forms such as SARS, MERS and 2019-nCoV can be lethal. Symptoms vary in other species: in chickens, they cause an upper respiratory disease, while in cows and pigs coronaviruses cause diarrhea. There are no vaccines or antiviral drugs to prevent or treat human coronavirus infections.

Coronaviruses are in the subfamily Orthocoronavirinae in the family Coronaviridae, in the order Nidovirales.[4][5] They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome 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 crown or of a 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. The name 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 crown or of a solar corona. This morphology is created by the viral spike (S) peplomers, which are proteins on the surface of the virus that 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

The infection cycle of coronavirus

After cell entry, the virus particle is uncoated and its genome enters the cell cytoplasm.

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

Coronavirus genomes also encodes a protein called a replicase which allows the 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, 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 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 cleave the polyprotein. This process is a form of genetic economy, allowing the virus 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.[11]

Taxonomy

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]

MERS-CoV, 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 SARS-CoV 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-CoV 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 proportion of all common colds in adults and children.[10] Coronaviruses cause colds with major symptoms, such as fever and sore throat from swollen adenoids, primarily in the winter and early spring seasons.[25] Coronaviruses can cause pneumonia – either direct viral pneumonia or a secondary bacterial pneumonia – and may 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 no vaccines or antiviral drugs to prevent or treat human coronavirus infections.[27]

Seven strains of human coronaviruses are known:

  1. Human coronavirus 229E (HCoV-229E)
  2. Human coronavirus OC43 (HCoV-OC43)
  3. Severe acute respiratory syndrome-related coronavirus (SARS-CoV)
  4. Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
  5. Human coronavirus HKU1
  6. Middle East respiratory syndrome-related coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC.
  7. Novel coronavirus (2019-nCoV),[28][29] also known as Wuhan coronavirus.[30] ('Novel' in this case means newly discovered, or newly originated, and is a placeholder name.)[29]

The coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and children world-wide.[31]

Characteristics of patients who have been infected with
2019-nCoV, MERS-CoV, and SARS-CoV[32]
2019-nCoV* MERS-CoV SARS-CoV
Demographic
Detection date December 2019 June 2012 November 2002
Detection place Wuhan, China Jeddah, Saudi Arabia Guangdong, China
Age average 49 56 39.9
Age range 21–76 14–94 1–91
Male:female ratio 2.7:1 3.3:1 1:1.25
Confirmed cases 835† 2494 8096
Case fatality rate 25† (2.9%) 858 (37%) 744 (10%)
Health-care workers 16‡ 9.8% 23.1%
Symptoms
Fever 40 (98%) 98% 99–100%
Dry cough 31 (76%) 47% 29–75%
Dyspnoea 22 (55%) 72% 40–42%
Diarrhoea 1 (3%) 26% 20–25%
Sore throat 0 21% 13–25%
Ventilatory support 9.8% 80% 14–20%
*: symptoms based on the first 41 patients. : Data as of 23 January 2020.
: Data as of 21 January 2020; other data up to 21 January 2020. Published on 24 January 2020


Severe acute respiratory syndrome (SARS)

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, the World 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). Over 8,000 people were infected, about 10% of whom died.[8]

Middle East respiratory syndrome

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).[33][34] The World Health Organization issued a global alert soon after.[35] The WHO update on 28 September 2012 stated that the virus did not seem to pass easily from person to person.[36] 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.[37] In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. 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 that the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus.[38] By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.[39]

After the Dutch Erasmus Medical Centre sequenced 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). In May 2014, the only two United States cases of MERS-CoV infection were recorded, both occurring in healthcare workers who worked in Saudi Arabia and then traveled to the U.S. One was treated in Indiana and one in Florida. Both of these individuals were hospitalized temporarily and then discharged.[40]

In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited 4 hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East.[41] 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%.[42]

Novel coronavirus (2019-nCoV)

Cross-sectional model of a coronavirus
Cross-sectional model of a coronavirus

In December 2019, a pneumonia outbreak was reported in Wuhan, China.[43] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[44] which was given the interim name 2019-nCoV by the World Health Organization (WHO).[28][29][45] Some researchers have suggested that the Huanan Seafood Market may not be the original source of viral transmission to humans.[46][47]

As of 10 February 2020, there have been 1,015 confirmed deaths and more than 42,850 confirmed cases in the coronavirus pneumonia outbreak.[48][49] The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with an ~70% genetic similarity to the SARS-CoV.[50] The virus was suspected to have originated in snakes,[51] but many leading researchers disagree with this conclusion.[52] The virus has a 96% similarity to a bat coronavirus, so an origin in bats is widely suspected.[46][53]

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.[54]

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.[55] 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 as ferret systemic coronavirus (FSC).[56] 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.[57] 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.[58]

A HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.[59]

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.[60]

In domestic animals

A new veterinary disease, porcine epidemic diarrhea virus (PED or PEDV), has emerged around the world.[citation needed] Its economic importance is unclear but shows high mortality in piglets.[citation needed]

See also

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Further reading

External links

Classification