The genetic structure of SARS-CoV-2 does not rule out a laboratory origin: SARS-COV-2 chimeric structure and furin cleavage site might be the result of genetic manipulation

Bioessays. 2021 Mar;43(3):e2000240. doi: 10.1002/bies.202000240. Epub 2020 Nov 17.


Severe acute respiratory syndrome-coronavirus (SARS-CoV)-2's origin is still controversial. Genomic analyses show SARS-CoV-2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS-CoV-2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS-like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat-derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site-directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS-CoV-2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS-CoV-2 origins.

Keywords: BtCov/4991; Gain-of-function studies; RaTG13; SARS-CoV-2; furin cleavage site; pangolin CoV; receptor binding domain.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Base Sequence
  • COVID-19 / pathology
  • COVID-19 / transmission*
  • COVID-19 / virology
  • China
  • Chiroptera / virology
  • Eutheria / virology
  • Furin / metabolism
  • Genetic Engineering / ethics*
  • Humans
  • Mutagenesis, Site-Directed / methods*
  • Protein Binding
  • Reassortant Viruses / genetics*
  • Reassortant Viruses / metabolism
  • Reassortant Viruses / pathogenicity
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity
  • Sequence Alignment
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / metabolism


  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • FURIN protein, human
  • Furin