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. (shrink)

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. (shrink)

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. (shrink)