"Abstract: To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident. The genome of SARS-COV-2 contains a peculiar pattern of unique restriction endonuclease recognition sites allowing efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses. Here, we report the likelihood of observing such a pattern in coronaviruses with no history of bioengineering. We find that SARS-CoV-2 is an anomaly, more likely a product of synthetic genome assembly than natural evolution. The restriction map of SARS-CoV-2 is consistent with many previously reported synthetic coronavirus genomes, meets all the criteria required for an efficient reverse genetic system, differs from closest relatives by a significantly higher rate of synonymous mutations in these synthetic-looking recognitions sites, and has a synthetic fingerprint unlikely to have evolved from its close relatives. We report a high likelihood that SARS-CoV-2 may have originated as an infectious clone assembled in vitro.
Lay Summary: ... We found that SARS-CoV has the restriction site fingerprint that is typical for synthetic viruses. The synthetic fingerprint of SARS-CoV-2 is anomalous in wild coronaviruses, and common in lab-assembled viruses. The type of mutations (synonymous or silent mutations) that differentiate the restriction sites in SARS-CoV-2 are characteristic of engineering, and the concentration of these silent mutations in the restriction sites is extremely unlikely to have arisen by random evolution. Both the restriction site fingerprint and the pattern of mutations generating them are extremely unlikely in wild coronaviruses and nearly universal in synthetic viruses. Our findings strongly suggest a synthetic origin of SARS-CoV2...
Introduction: ... There are currently two hypotheses on the origin of SARS-CoV-2. The first hypothesis posits that SARS-CoV-2 has a natural origin and spilled over from animals to people at the Huanan seafood market (Pekar et al. 2022; Worobey et al. 2022)...
The second hypothesis on the origin of SARS-CoV-2 posits that SARS-CoV-2 originated in a lab as a result of coronavirus (CoV) research. The lab origin hypothesis primarily notices that CoV research was carried out in Wuhan and that SARS-CoV-2 is unique among sarbecoviruses in having a Furin cleavage site (FCS) between the S1 and S2 subunits of the Spike protein. In-vitro studies have found the FCS is key to SARS-CoV-2 pathogenesis (Johnson et al. 2021)."
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