Chat message

Slack / Private Message Drop, p.29 [SLACK_000243] · slack_pm:msg:00298

Date: 2020-05-18 17:46
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen
Topics: Furin cleavage site and molecular features Natural origin / zoonotic spillover

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When it comes to the selection argument, what is still most telling to be is the RBD. SARS changed the contact residues a lot getting into humans, so a lot of the signal might have been driven by that. SARS-CoV-2 is already'perfect' for binding, so it doesn't need to - BUT that 'perfect' RBD is found in a pangolin CoV, so clearly it already exists in nature - no further adaptation needed it seems.

Extracted statements

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Statement	Grade	Attribution	Stance
When it comes to the selection argument, what is still most telling to be is the RBD.	needs context	speaker_own	asserts
SARS-CoV-2 is already'perfect' for binding, so it doesn't need to - BUT that 'perfect' RBD is found in a pangolin CoV, so clearly it already exists in nature - no further adaptation needed it seems.	needs context	uncertain explicit hedge	asserts

Statement

Grade

Attribution

Stance

When it comes to the selection argument, what is still most telling to be is the RBD.

needs context

speaker_own

asserts

SARS-CoV-2 is already'perfect' for binding, so it doesn't need to - BUT that 'perfect' RBD is found in a pangolin CoV, so clearly it already exists in nature - no further adaptation needed it seems.

needs context

uncertain explicit hedge

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

2020-05-18 16:51 Kristian G. Andersen open

@Eddie Holmes - your questions earlier last week, were they referring to this paper? https://www.biorxiv.org/content/10.1101/2020.05.01.073262v1 I find it to be quite interesting and they pick up on some of the exact features of (lack of) selection that I reported back in February. Certainly peculiar - and I think lends _some_ evidence to the pre-circulation theory.
2020-05-18 16:53 Kristian G. Andersen open

Back in February I compared S and ORF1 - so just here for reference (very similar to what they observe) [shared file(s): Screen Shot 2020-05-18 at 4.52.06 PM.png]
2020-05-18 17:40 Edward C. Holmes open

No, they weren't. I asked some questions by my friends who drive cars with blacked out windows if you know what Imean. I saw that paper and of course reminded me of your earlier analysis. Not quite sure what to think: that paperis deliberately trying to be controversial by not excluding lab escape. But would lab culturing have produced a'perfectly' adapted human virus? I don't see way. Did the 2013-2016 EBOV require any human adaptation?
2020-05-18 17:42 Kristian G. Andersen open

"lab culturing have produced a 'perfectly' adapted human virus" - I'm not quite sure. I would think not (outside the spike), but it depends on what drives the selection and that is unclear to me.We both have papers on Ebola human adaptation, so I'd say yes :wink:
2020-05-18 17:46 Kristian G. Andersen

When it comes to the selection argument, what is still most telling to be is the RBD. SARS changed the contact residues a lot getting into humans, so a lot of the signal might have been driven by that. SARS-CoV-2 is already'perfect' for binding, so it doesn't need to - BUT that 'perfect' RBD is found in a pangolin CoV, so clearly it already exists in nature - no further adaptation needed it seems.
2020-05-18 17:48 Kristian G. Andersen open

Re. Ebola - also in the Park et al., paper: https://www.cell.com/action/showPdf?pii=S0092-8674%2815%2900690-X [shared file(s): Screen Shot 2020-05-18 at 5.48.09 PM.png, Screen Shot 2020-05-18 at 5.47.34 PM.png]
2020-05-18 18:16 Edward C. Holmes open

But A82V occurred after the virus had been spreading for a while in humans during that outbreak. The key point was virus was ready to go as it emerged it humans. Completely agree about the pangolin RBD.

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