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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Viewpoint: Origin of SARS-CoV-2.

Kenneth Lundstrom1, Murat Seyran2,3, Damiano Pizzol4

  • 1PanTherapeutics, CH1095 Lutry, Switzerland.

Viruses
|October 27, 2020
PubMed
Summary

The precise origin of SARS-CoV-2 remains undetermined, with research exploring natural selection in animal hosts or humans post-zoonotic transfer. Further investigation is needed to confirm the virus

Keywords:
COVID-19 pandemiccoronavirusgenome homologynatural selectionorigin of SARS-CoV-2receptor binding domainzoonotic transfer

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Area of Science:

  • Virology
  • Genomics
  • Epidemiology

Background:

  • The origin of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, is not fully elucidated.
  • While bat coronavirus RaTG13 is a likely precursor, discrepancies in host tropism and specific protein domains (S protein receptor-binding domain, N-terminal domain, sialic acid-binding domain) exist compared to other human coronaviruses.
  • SARS-CoV-2 exhibits enhanced stability and binding affinity to the human ACE2 receptor, despite structural similarities identified through cryo-electron microscopy and biochemical studies.

Discussion:

  • Laboratory manipulation is considered highly unlikely as a source for SARS-CoV-2.
  • Two primary hypotheses for SARS-CoV-2 origin are proposed: natural selection in an animal reservoir before zoonotic transfer, or adaptation through human-to-human transmission after zoonotic transfer.
  • Pangolin coronaviruses show significant similarity, particularly in the receptor-binding domain, supporting the pre-zoonotic transfer natural selection hypothesis.

Key Insights:

  • The SARS-CoV-2 genome does not display a prominent mutational "hot spot," with D614G being the most identified mutation in clinical isolates.
  • Evidence suggests that isolated SARS-CoV-2 genomes share a common origin, irrespective of the specific evolutionary pathway.
  • Comparative genomic analysis reveals distinct features in SARS-CoV-2's interaction with the ACE2 receptor.

Outlook:

  • Further research is essential to definitively confirm the origin of SARS-CoV-2.
  • Investigating the evolutionary dynamics of coronaviruses in both animal and human populations will be crucial.
  • Continued surveillance and genomic sequencing of emerging coronaviruses are necessary for pandemic preparedness.