Slack / Private Message Drop — page 69

[Kristian Andersen] While I knew about the furin site insertion experiments, I did know realize this (that the insertion in SARS2 is exactly where they inserted it experimentally in SARS): https://twitter.com/Ayjchan/status/1266805310313967617?s=20 [2020-06-11 13:35:58] [Kristian Andersen] Gotta say - some smoking(ish) guns starting to appear that I'm not comfortable with and Alina here is touching on a lot of points we have discussed previously that were concerning (e.g., lack of selection - I should have looked into that a little closer earlier :wink: ). The furin site in SARS2 is exactly the same as it is in some of the HKU1 sequences. When I talked to Farzan way back in the day he mentioned that the one thing he'd be looking for was whether SARS2 would lose the furin site under different conditions - we now know this to be true (primarily in T/C, but there are examples in people too - intrahost). [2020-06-11 13:58:46] [Robert Garry] "exactly where they inserted it experimentally in SARS" Sure - but that site with the single R is a required cleavage site - if you're going to convert to a furin site then adding RRA at that exact position is the only thing that makes sense - or even RRAR to make it a super-optimal site like Nunberg did - what would not make sense is to stick a proline in and then to do the whole insertion out-of-frame. [2020-06-11 14:08:35] [Kristian Andersen] Yeah, agreed - however, this exact site already exist in other CoVs (just not in exactly this site) - not in HKU1 as I said, but in that Feline CoV. The part I'm really struggling with is that at the end of the day, we really don't have any hard evidence one way or the other - and especially given some of the recent evidence, we also can't rule out that somebody actually put it in there. That's obviously not to say that somebody _*did*_, but we can't rule it out. Our paper was pretty strong in saying "there's no way", but I have less confidence in that statement at this stage. [2020-06-11 14:33:23] [Eddie Holmes] What smoking guns Kristian? I don't quite see it. What recent evidence are you talking about? That Follis paper was literally the first one I looked at. Doesn't it's presence in HKU1 suggest that these events in nature a lot? Do we know what animal HKU1 comes from? I was reading Mike's paper to suggest that D614G was under selection to increase the infectivity of SARS-CoV-2, because it was directly related to the furin cleavage insertion, such that it not perfectly adapted to humans on emergence. [2020-06-11 14:33:34] [Eddie Holmes] What about Bill Gallaher's evidence? [2020-06-11 14:34:14] [Robert Garry] HKU1 actually does have an optimal furin site - some strains have a insert or deletion of SSS - yes some of these S have predicted O-glycans [shared file(s): HKU-1 Spike.pdf] [2020-06-11 14:38:27] [Robert Garry] "animal HKU1 comes from" Rodents maybe - probably [2020-06-11 14:44:30] [Eddie Holmes]