The genetic structure of SARS‐CoV‐2 is consistent with both natural or laboratory origin: Response to Tyshkovskiy and Panchin (10.1002/bies.202000325)

Abstract

Tyshkovskiy and Panchin have recently published a commentary on our paper in which they outline several "points of disagreement with the Segreto/Deigin hypothesis." As our paper is titled "The genetic structure of SARS-CoV-2 does not rule out a laboratory origin," points of disagreement should provide evidence that rules out a laboratory origin. However, Tyshkovskiy and Panchin provide no such evidence and instead attempt to criticize our arguments that highlight aspects of SARS-CoV-2 that could be consistent with the lab leak hypothesis. Strikingly, Tyshkovskiy and Panchin's main point of criticism is based on a false premise that we have claimed RaTG13 to be a direct progenitor of SARS-CoV-2, and their other points of criticism are either not valid, based on flawed mathematical analysis, or are unrelated to our hypotheses. Thus, the genetic structure of SARS-CoV-2 remains consistent with both natural or laboratory origin, which means that both the zoonotic and the lab leak hypothesis need to be investigated equally thoroughly.

There is still no evidence of SARS‐CoV‐2 laboratory origin: Response to Segreto and Deigin (10.1002/bies.202100137)

“…The authors responded that: "we never claim that RaTG13 itself is a 'proposed ancestor' or the backbone used for a possible construction of SARS-CoV-2″ and emphasized that their hypothesis was about a "RaTG13-like backbone and an RBD from a MP789-like pangolin CoV". [2] Although the authors didn't claim that RaTG13 itself was an ancestor of SARS-CoV-2 in their article in Bioessays, they explicitly and repeatedly stated that in other resources, including their online blogs: "And CoV2 is an obvious chimera (though not nesessarily a lab-made one), which is based on the ancestral bat strain RaTG13, in which the receptor binding motif (RBM) in its spike protein is replaced by the RBM from a pangolin strain, and in addition, a small but very special stretch of four amino acids is inserted, which creates a furin cleavage site that, as virologists have previously established, significantly expands the "repertoire" of the virus in terms of whose cells it can penetrate". [11] Remarkably, the blog post hasn't been corrected after our commentary as we are writing this response.…”

“…In the end, the authors concluded that we have "underestimated the probability of a 12-nt insertion not containing a 5+ restriction enzyme cut site by 2 orders of magnitude: rather than the 0.5% implied by their [our] calculation, the actual probability is around 50%". [2] We could discuss which statistical models and assumptions are more reasonable in the given circumstances. However, this is not necessary, since the smallest probability achieved by Segreto and Deigin in their own calculation (p = 0.468) is still far higher, by an order of magnitude, than the relaxed threshold (p = 0.05) used to reject the null hypothesis in statistical analysis.…”

“…The authors responded that: “we never claim that RaTG13 itself is a ‘proposed ancestor’ or the backbone used for a possible construction of SARS‐CoV‐2″ and emphasized that their hypothesis was about a “RaTG13‐like backbone and an RBD from a MP789‐like pangolin CoV”. [ 2 ]…”

“…Commenting the hypothesis of bat origin of SARS‐CoV‐2, Segreto and Deigin state that the RBD of the coronavirus is “peculiar because it is characterized by a very high binding affinity to the human ACE2 receptor, but it binds poorly to the bat ACE2 receptor”. [ 2 ] However, the reference used by the authors to support this claim is not an experimental study but a computational analysis of SARS‐CoV‐2 binding to various vertebrate ACE2 receptors. [ 21 ] Moreover, several crucial experimental studies conducted afterwards appear to challenge this claim.…”

“…Some proponents of the lab origin hypothesis including Segreto and Deigin have claimed that the genome of the coronavirus (CoV) has certain features "which could be consistent with a lab origin", including (i) the similarity of the SARS-CoV-2 backbone and receptor binding domain (RBD) with the backbone of bat CoV RaTG13 and RBD of pangolin CoV MP789 respectively, and (ii) the presence of a 12 nucleotide insertion that resulted in a formation of S1/S2 furin cleavage site (FCS). [1,2] Even though the authors themselves admit that these observations are also consistent with the scenario of natural emergence, that is, "the genetic structure of SARS-CoV-2 is consistent with both natural or laboratory origin", they use it as an argument for the hypothesis of SARS-CoV-2 artificial creation.…”