Might SARS-CoV-2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?: A potential explanation for much of the novel coronavirus' distinctive genome

Bioessays. 2020 Oct;42(10):e2000091. doi: 10.1002/bies.202000091. Epub 2020 Aug 12.

Abstract

Despite claims from prominent scientists that SARS-CoV-2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy-makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behavior. Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual-use gain-of-function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS-CoV-2's distinctive spike-protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus's origins and a re-examination of the risks and rewards of dual-use gain-of-function research.

Keywords: COVID-19; SARS-CoV-2; coronavirus; gain-of-function; intermediate host; pandemic; serial passage; virology.

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / genetics*
  • Betacoronavirus / growth & development
  • COVID-19
  • Coronavirus Infections / etiology*
  • Coronavirus Infections / transmission*
  • Gain of Function Mutation / genetics
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / etiology*
  • Pneumonia, Viral / transmission*
  • Protein Binding
  • SARS-CoV-2
  • Serial Passage
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Zoonoses / transmission*
  • Zoonoses / virology

Substances

  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2