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.
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.
Pangolins are the only animals other than bats proposed to have been infected with SARS-CoV-2related coronaviruses (SARS2r-CoVs) prior to the COVID-19 pandemic. Here we examine thenovel SARS2r-CoV we previously identified in game animal metatranscriptomic datasetssequenced by He et al. (2022) and find that sections of the partial genome phylogenetically groupwith Guangxi (GX) pangolin CoVs (GX PCoVs), while the full RdRp sequence groups with bat-SL-CoVZC45. While the novel SARS2r-CoV is found in 6 pangolin datasets, the same CoV isalso found in 10 additional NGS datasets from 5 separate mammalian species and is likelyrelated to contamination by a laboratory researched virus. Absence of bat mitochondrialsequences from the datasets, the fragmentary nature of the virus sequence and the presence of apartial sequence of a cloning vector attached to a SARS2r-CoV read suggests that it has beencloned. We find that NGS datasets containing the novel SARS2r-CoV are contaminated withsignificant Homo sapiens genetic material, and numerous viruses not associated with the hostanimals sampled. We further identify the dominant human haplogroup of the contaminatingH.sapiens genetic material to be F1c1a1, which is of East Asian provenance. The association ofthis novel CoV with both bat CoV and the Guangxi pangolin CoV (GX PCoV) clades is animportant step towards identifying the origin of the GX PCoVs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.