Coronavirus

Coronaviruses are a group of viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that are typically mild, such as the common cold, though rarer forms such as SARS, MERS and COVID-19 can be lethal. Symptoms vary in other species: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are no vaccines or antiviral drugs to prevent or treat human coronavirus infections.

Coronaviruses comprise the subfamily Orthocoronavirinae in the family Coronaviridae, in the order Nidovirales.[5][6] 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 27 to 34 kilobases, the largest among known RNA viruses.[7] 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.[8] 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.[9] 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 SARS-CoV-2 (formerly known as 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).[10] Some coronaviruses (specifically the members of Betacoronavirus subgroup A) also have a shorter spike-like protein called hemagglutinin esterase (HE).[5]

Replication

The infection cycle of a coronavirus
After entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.[11]

The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail, which allows the RNA to attach to the host cell’s ribosome for translation.[12]

Coronavirus genomes also encode a protein called RNA-dependent RNA polymerase (RdRp), which allows the viral genome to be transcribed into new RNA copies using the host cell’s machinery. The RdRp is the first protein to be made; once the gene encoding the RdRp 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.[citation needed] Coronavirus non-structural proteins provide extra fidelity to replication, because they confer a proofreading function, which is lacking in RNA-dependent RNA polymerase enzymes alone.[13]

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.[14]

Transmission

Human to human transmission of coronaviruses is primarily thought to occur among close contacts via respiratory droplets generated by sneezing and coughing.[15]

Taxonomy

For a more detailed list of members, see Coronaviridae.
The scientific name for coronavirus is Orthocoronavirinae or Coronavirinae.[2][3][4] Coronavirus belongs to the family of Coronaviridae.

  • Genus: Alphacoronavirus
    • Species: 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, Severe acute respiratory syndrome-related coronavirus, Tylonycteris bat coronavirus HKU4, Middle East respiratory syndrome-related coronavirus, Human coronavirus OC43, Hedgehog coronavirus 1 (EriCoV)

     

    • Genus Gammacoronavirus; type species: Infectious bronchitis virus
      • Species: Beluga whale coronavirus SW1, Infectious bronchitis virus

     

    • Genus Deltacoronavirus; type species: Bulbul coronavirus HKU11
        • Species: Bulbul coronavirus HKU11, Porcine coronavirus HKU15,

          Evolution

          The most recent common ancestor (MRCA) of all coronaviruses has been placed at around 8000 BCE.[16] The MRCAs 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. It appears that bats and birds, as 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.[17]

          Bovine coronavirus and canine respiratory coronaviruses diverged from a common ancestor in 1951.[18] Bovine coronavirus and human coronavirus OC43 diverged around the 1890s. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century.[19]

          The MRCA of human coronavirus OC43 has been dated to the 1950s.[20]

          MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.[21] The human coronavirus NL63 and a bat coronavirus shared an MRCA 563–822 years ago.[22]

          The most closely related bat coronavirus and SARS-CoV diverged in 1986.[23] A path of evolution of the SARS virus and keen relationship with bats have been proposed.[24][25] 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.[26]

          Human coronaviruses

          Coronaviruses are believed to cause a significant proportion of all common colds in adults and children.[14] Coronaviruses cause colds with major symptoms, such as fever and sore throat from swollen adenoids, primarily in the winter and early spring seasons.[27] 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.[28] 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.[28] There are no vaccines or antiviral drugs to prevent or treat human coronavirus infections.[29]

          Seven strains of human coronaviruses are known:

          Human coronavirus 229E (HCoV-229E)
          Human coronavirus OC43 (HCoV-OC43)
          Severe acute respiratory syndrome 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
          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019-nCoV or “novel coronavirus 2019”
          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]

          Outbreaks of coronavirus-related diseases

           

          Severe acute respiratory syndrome (SARS)
          Main article: Severe acute respiratory syndrome
          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.[10]

          Middle East respiratory syndrome (MERS)
          Main article: 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).[36][37] The World Health Organization issued a global alert soon after.[38] The WHO update on 28 September 2012 stated that the virus did not seem to pass easily from person to person.[39] 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.[40] 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.[41] By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.[42]

          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.[43]

          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.[44] 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%.[45]

          Coronavirus disease 2019 (COVID-19)
          Main article: Coronavirus disease 2019

          Cross-sectional model of a coronavirus
          In December 2019, a pneumonia outbreak was reported in Wuhan, China.[46] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[47] which was given the interim name 2019-nCoV by the World Health Organization (WHO),[48][49][50] later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses. Some researchers have suggested that the Huanan Seafood Market may not be the original source of viral transmission to humans.[51][52]

          As of 27 February 2020, there have been 2,810 confirmed deaths and more than 82,500 confirmed cases in the coronavirus pneumonia outbreak.[53][54] The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with an ~70% genetic similarity to the SARS-CoV.[55] The virus has a 96% similarity to a bat coronavirus, so an origin in bats is widely suspected.[51][56]

          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.[58]

          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.[59] 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).[60] 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.[61] 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.[62]

          A HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.[63]

          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.[64]

          In domestic animals
          Infectious bronchitis virus (IBV) causes avian infectious bronchitis.
          Porcine coronavirus (transmissible gastroenteritis coronavirus of pigs, TGEV).[65][66] Bovine coronavirus (BCV), responsible for severe profuse enteritis in of young calves.
          Feline coronavirus (FCoV) causes mild enteritis in cats as well as severe Feline infectious peritonitis (other variants of the same virus).
          the two types of canine coronavirus (CCoV) (one causing enteritis, the other found in respiratory diseases).
          Turkey coronavirus (TCV) causes enteritis in turkeys.
          Ferret enteric coronavirus causes epizootic catarrhal enteritis in ferrets.
          Ferret systemic coronavirus causes FIP-like systemic syndrome in ferrets.[67] Pantropic canine coronavirus.
          Rabbit enteric coronavirus causes acute gastrointestinal disease and diarrhea in young European rabbits. Mortality rates are high.[68] Porcine epidemic diarrhea virus (PED or PEDV), has emerged around the world.[69]

          Genomic cis-acting elements

          In common with the genomes of all other RNA viruses, coronavirus genomes contain cis-acting RNA elements that ensure the specific replication of viral RNA by a virally encoded RNA-dependent RNA polymerase. The embedded cis-acting elements devoted to coronavirus replication constitute a small fraction of the total genome, but this is, it is presumed, a reflection of the fact that coronaviruses have the largest genomes of all RNA viruses. The boundaries of cis-acting elements essential to replication are fairly well-defined, and an increasingly well-resolved picture of the RNA secondary structures of these regions is emerging. However, we are in only the early stages of understanding how these cis-acting structures and sequences interact with the viral replicase and host cell components, and much remains to be done before we understand the precise mechanistic roles of such elements in RNA synthesis.[70][5]

      Genome packaging

      The assembly of infectious coronavirus particles requires the selection of viral genomic RNA from a cellular pool that contains an abundant excess of non-viral and viral RNAs. Among the seven to ten specific viral mRNAs synthesized in virus-infected cells, only the full-length genomic RNA is packaged efficiently into coronavirus particles. Studies have revealed cis-acting elements and trans-acting viral factors involved in coronavirus genome encapsidation and packaging. Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies and viral expression vectors based on the coronavirus genome.[70][5]

      The Credit Risk (Ofer Abarbanel online library)