There is no evidence of SARS-CoV-2 laboratory origin: Response to Segreto and Deigin (DOI: 10.1002/bies.202000240)

Abstract

The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the subject of many hypotheses. One of them, proposed by Segreto and Deigin, assumes artificial chimeric construction of SARS-CoV-2 from a backbone of RaTG13-like CoV and receptor binding domain (RBD) of a pangolin MP789-like CoV, followed by serial cell or animal passage. Here we show that this hypothesis relies on incorrect or weak assumptions, and does not agree with the results of comparative genomics analysis. The genetic divergence between SARS-CoV-2 and both its proposed ancestors is too high to have accumulated in a lab, given the timeframe of several years. Furthermore, comparative analysis of S-protein gene sequences suggests that the RBD of SARS-CoV-2 probably represents an ancestral non-recombinant variant. These and other arguments significantly weaken the hypothesis of a laboratory origin for SARS-CoV-2, while the hypothesis of a natural origin is consistent with all available genetic and experimental data.

Keywords: COVID-19; SARS-CoV-2; SARS-CoV-2 laboratory origin; comparative genomics; coronavirus; evolution; furin cleavage site.

FIGURE 1

Relative frequencies of different single nucleotide substitutions, which distinguish SARS‐CoV‐2 (red) and SARS‐CoV (blue) from their bat relatives (RaTG13 and Rs4231, respectively).^{[ 7 ]} Differences across substitution frequencies are not significant, as assessed with Pearson's chi‐squared test (p = 0.12)

FIGURE 2

Multiple alignment of S‐protein gene RBD sequences of SARS‐CoV‐2, Pangolin CoV MP789 and RaTG13

FIGURE 3

500‐nucleotide sequence map around the furin cleavage site with some of the restriction sites corresponding to commercially available restriction enzymes. Sites cleaved with blunt, 5′‐extended and 3′‐extended ends are shown in red, blue, and green, respectively