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0. A huge disservice to the genuine Q of Sars2 = lab manip. vs wild-borne. It ignores a mountain of evidence generated over the last year supporting a natural origin. Instead it straw mans arguments made a year ago, ignoring today - a thread https://nicholaswade.medium.com/origin-of-covid-following-the-clues-6f03564c038
1. No evidence presented for the lab release hypothesis. Only accusations that assume CoV scientists as bad-faith actors covering up Chinese conspiracy. Note: barring manipulation, the proposal of lab-release vs nat. origin is the same: humans went out, got Sars2, brought it back
2. The lengthy discussion of seamless editing etc... is a dogwhistle. Evol biologists are expert at detecting recombination. If the Spike had a clear origin, we'd be able to say "it was a recomb between RaTG13 and MERS Spike."
2. cont: It's not like the closest relative is 96% similar and we just haven't realized the source of a recombination that causes a 4% overall divergence. It's just a unique virus. https://www.nature.com/articles/s12276-021-00604-z
3. The RRAR furin site argument is incorrect and illogical. Many CoVs have furin sites. Furin motifs are RXn(K/R)R. Not PRRA as the author purports. If anything, Prolines are sticky-outy in a way that inhibits furin, and they're uncommon around furin motifs. doi:10.1002/cti2.1073
3. cont: However see this interesting preprint suggesting the Proline mediates O-glycosylation of Sars2 spike. Not something we'd build-in, but certainly something that could explain this Proline. https://www.biorxiv.org/content/10.1101/2021.02.05.429982v1.full
3. cont2: That also said. one of the variant mutations replaces the Proline (P681Y). So we'll have to wait and see if this Proline is really a helpful site for Sars2 spread in humans.
4. The idea of serial passage as an origin story is ridiculous. We know that after only a few passages, the virus accumulates many SNPs. This makes sense, in vitro lacks adaptive immunity, and we relax selection. A virus adapted for a cell line is rapidly attenuated.
