The virus: SARS-CoV-2

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A member of the coronavirus family

Coronaviruses are RNA viruses of zoonotic origin. Most human-hosted coronaviruses are capable of causing “common cold”-type symptoms, such as sore throat, stuffy or runny nose, coughing, and/or sneezing.[1]
However, some notable exceptions have resulted in outbreaks of severe respiratory diseases in the 21st century: SARS (2002), MERS (2012), and now COVID-19 (2019 to present).[2],[3]
Infection with the SARS-CoV-2 coronavirus is the known cause of the potentially fatal respiratory disease known as COVID-19.[4],[5]

The SARS-CoV-2 virus structure

SARS-CoV-2 is a single-stranded, positive-sense RNA virus (a virus whose genetic information consists of a single strand of RNA encoding viral proteins) with a genome that encodes 4 major structural proteins.[2]
These 4 proteins are all required to produce infectious virions capable of replication:

  • Spike protein (S), which mediates viral binding to and entry into cells
  • Nucleocapsid protein (N), which houses the genetic material (RNA)
  • Envelope protein (E) and membrane protein (M), which are required for organization and assembly of infectious virions[2]

Like all RNA viruses (such as influenza A virus strains, which cause seasonal flu), SARS-CoV-2 has a higher mutation rate than DNA viruses (such as papilloma viruses which can cause warts, other skin lesions, and/or cancers; and herpes viruses which can cause chicken pox, cold sores, and/or encephalitis), resulting in increased genetic diversity. This results in a range of viral genetic variant sub-populations (known as quasispecies) with different viral fitness profiles (i.e., the ability to adapt and replicate) and potential for infection and disease virulence.[6],[7]

The D614G SARS-CoV-2 spike protein (S)[6],[8]

The D614G SARS-CoV-2 spike protein (S) variant is the most common viral variant observed in mutational analyses reported in the literature.[6],[8]
Genomic analyses of SARS-CoV-2 isolates have identified thousands of viral variants, including those that have been associated with increased COVID-19-related mortality. However, the viral variant garnering the most attention from researchers is the D614G spike protein (S) variant. 

  • D614G is the most common variant observed in mutational analyses reported in the literature.[6],[8]
  • The D614G mutation reportedly increases the infectivity of SARS-CoV-2.[6]
  • Isolates of SARS-CoV-2 encoding the D614G mutation have been demonstrated to predominate over time in multiple geographic locations, including the European Union, China, and the U.S., implying that this change enhances viral transmission.[8],[9]
  • D614G has also been correlated with increased viral loads in COVID-19 patients.[9]
  • In an analysis of over 46,000 SARS-CoV-2 assemblies from almost 100 countries across the globe, a total of 12,706 mutations were identified, the majority of which were C→U transitions.[10] Over 36,000 of the assemblies in the data set (77.8%) analyzed carried the derived allele from the D614G mutation.[10]

References

  1. The Institute for Quality and Efficiency in Health Care (IQWiG). InformedHealth.org. National Center for Biotechnology Information (NCBI) website. https://www.ncbi.nlm.nih.gov/books/NBK279543/. Common colds: Overview. Updated October 8, 2020. Accessed October 29, 2020.
  2. Su S, et al. Trends Microbiol. 2016;24:490-502.
  3. Rasmussen SA, et al. Microbiol Spectrum 2016;4. doi: 10.1128/microbiolspec.EI10-0020-2016.
  4. Toyoshima Y, et al. J Human Genet. 2020;1-8. doi: 10.1038/s10038-020-0808-9.[Epub ahead of print]
  5. Pachetti, M, et al. J Transl Med. 2020;18:179.
  6. Korber B, et. Cell. 2020;182:812-827.
  7. Domingo E, Perales C. PLoS Genet. 2019;15(10):e1008271.
  8. Koyama T, et al. Bull World Health Organ. 2020;98:495-504.
  9. Zhang L, et al. bioRxiv. 2020. doi: 10.1101/2020.06.12.148726.[Preprint]
  10. van Dorp L, et al. Nat Commun 2020;11:5986.

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