More than a year after the initial documented cases in Wuhan, the source of SARS-CoV-2 has yet to be identified, and the search for a direct or intermediate host in nature has been so far unsuccessful.
The low binding affinity of SARS-CoV-2 to bat ACE2 studied to date does not support Chiroptera as a direct zoonotic agent. Furthermore, the reliance on pangolin coronavirus receptor binding domain (RBD) similarity to SARS-CoV-2 as evidence for natural zoonotic spillover is flawed, as pangolins are unlikely to play a role in SARS-CoV-2′s origin and recombination is not supported by recent analysis.
At the same time, genomic analyses pointed out that SARS-CoV-2 exhibits multiple peculiar characteristics not found in other Sarbecoviruses.
A novel multibasic furin cleavage site (FCS) confers numerous pathogenetically advantageous capabilities, the existence of which is difficult to explain though natural evolution...
source: https://link.springer.com/article/10.1007/s10311-021-01211-0
> https://www.sciencedirect.com/science/article/pii/S187350612...
They exist in the human HCoV-HKU1, HCoV-OC43, MERS-CoV and appear to have evolved independently at least 6 times in betacoronaviruses.
Furthermore while this article claims that the furin cleavage site has not found in any sarbecoviruses, that is now outdated information:
> "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia"
> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/
Both RacCS203 (91.5% similar to SARS-CoV-2) and RmYN02 (93.3% similar to SARS-CoV-2) have furin cleavage sites. So we're up to 7-to-9 times now that evolution has evolved a furin cleavage site in betacoronaviruses, including 3 sarbecoviruses that may or may not be directly related.
The whole "furin cleavage site is an indication of human engineering" argument is just falsified at this point.
I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still seems to me like it points weakly (at least 3x prevalence?) towards lab origin, though.
The significance is zero. Nature itself knows how to figure it out.
> but rare among such viruses in nature.
This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles.
We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SARS-CoV-2) in bats in Thailand which have an FCS.
It points literally 0% towards lab origin.