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Slack / Private Message Drop, pp.261-262 [SLACK_000475] · slack_pm:msg:02731

Date: 2020-11-17 10:03
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features

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Some wild speculation if you want to "connect" 69/70 to 453. MERS-CoV uses both [either?] a protein and a sialicacid receptor. HKU1 uses sialic acid and of course SARS CoVs use ACE2. What's not known [here's the speculation] is if the NTD of SARS-CoV2 (where the 69/70 deletion is actually part of a receptor binding domain forsialic acid or other molecule. If so a deletion in the NTD affecting binding to this receptor might affect entry driven bythe CTD. Receptor swapping is definitely a thing in HIV (chemokine receptors). [shared file(s): image.png]

Extracted statements

Rule-extracted, not adjudicated. The grade says what may be done with each one; read the document above before relying on any of them.

Statement	Grade	Attribution	Stance
What's not known [here's the speculation] is if the NTD of SARS-CoV2 (where the 69/70 deletion is actually part of a receptor binding domain forsialic acid or other molecule.	needs context	speaker_own	asserts

Statement

Grade

Attribution

Stance

What's not known [here's the speculation] is if the NTD of SARS-CoV2 (where the 69/70 deletion is actually part of a receptor binding domain forsialic acid or other molecule.

needs context

speaker_own

asserts

In context

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

2020-11-17 09:21 Kristian G. Andersen open

Thanks Andrew for sharing - very interested to get your insights into this. Will keep confidential - A LOT of disagreement in DK about how to handle that (most of those discussions driven by people that have no background in any of this...).
2020-11-17 09:26 Andrew Rambaut open

We (WHO working group) did talk to the SSI but they were very cagy (as you might expect). But they sharing isolates now through the WHO I believe.
2020-11-17 09:42 Robert F. Garry open

FWIW - the 69/70 S deletion comes at a region that is disordered at least in some spike structures (reddish sphereshere). It's at the top of the spike but not close by to Y453 (bluish) so not obvious why the might be linked. Not likesubstructures that interact (for example the 6 helix bundles) where you expect compensatory/complementarymutations. [shared file(s): image.png]
2020-11-17 09:50 Kristian G. Andersen open

> We (WHO working group) did talk to the SSI but they were very cagy (as you might expect). But they sharing isolates now through the WHO I believe. Yup, no surprise there - unfortunately. And yes - I believe they have shared the isolates widely now (including withUS) labs, so hopefully we'll learn more soon. I think they got a little surprised by how strongly the scientific community pushed back at them for not releasing data, so hopefully they have learned a lesson. (unfortunately way too much focus has been put on the mistakes here though - it's really important we remember that the main issue here is a parallel (raging) epidemic in mink).
2020-11-17 10:03 Robert F. Garry

Some wild speculation if you want to "connect" 69/70 to 453. MERS-CoV uses both [either?] a protein and a sialicacid receptor. HKU1 uses sialic acid and of course SARS CoVs use ACE2. What's not known [here's the speculation] is if the NTD of SARS-CoV2 (where the 69/70 deletion is actually part of a receptor binding domain forsialic acid or other molecule. If so a deletion in the NTD affecting binding to this receptor might affect entry driven bythe CTD. Receptor swapping is definitely a thing in HIV (chemokine receptors). [shared file(s): image.png]
2020-11-17 10:03 Robert F. Garry open

and now @Kristian Andersen i'll get back to my project1 report

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