SARS-CoV-2's claimed natural origin is undermined by issues with genome sequences of its relative strains: Coronavirus sequences RaTG13, MP789 and RmYN02 raise multiple questions to be critically addressed by the scientific community

Bioessays. 2021 Jul;43(7):e2100015. doi: 10.1002/bies.202100015. Epub 2021 May 27.

Abstract

RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2's origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.

Keywords: Pangolin CoV MP789; RaTG13; RmYN02; SARS-CoV-2; furin cleavage site; origin; peer review.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / epidemiology
  • COVID-19 / transmission
  • COVID-19 / virology*
  • Chiroptera / virology*
  • Datasets as Topic
  • Furin / metabolism
  • Humans
  • Pandemics
  • Pangolins / virology*
  • Phylogeny
  • SARS Virus / classification
  • SARS Virus / genetics*
  • SARS Virus / isolation & purification
  • SARS-CoV-2 / classification*
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / isolation & purification
  • Sequence Deletion / genetics
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Uncertainty*
  • Viral Zoonoses / transmission
  • Viral Zoonoses / virology

Substances

  • Spike Glycoprotein, Coronavirus
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Furin