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Slack / Private Message Drop, pp.68-69 [SLACK_000282] · slack_pm:msg:00698

Date: 2020-06-11 13:31
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen
Topics: Furin cleavage site and molecular features

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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

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Statement	Grade	Attribution	Stance
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	needs context	speaker_own	questions

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needs context

speaker_own

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2020-06-11 13:31 Kristian G. 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 Kristian G. Andersen open

Gotta say - some smoking(ish) guns starting to appear that I'm not comfortable with and Alina here is touching on alot 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 Robert F. Garry open

"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 aproline in and then to do the whole insertion out-of-frame.
2020-06-11 14:08 Kristian G. Andersen open

Yeah, agreed - however, this exact site already exist in other CoVs (just not in exactly this site) - not in HKU1 as Isaid, 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 orthe other - and especially given some of the recent evidence, we also can't rule out that somebody actually put it inthere. That's obviously not to say that somebody _*did*_, but we can't rule it out. Our paper was pretty strong insaying "there's no way", but I have less confidence in that statement at this stage.
2020-06-11 14:33 Edward C. Holmes open

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.

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