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Slack / Private Message Drop, pp.348-349 [SLACK_000562] · slack_pm:msg:03665

Date: 2020-12-30 14:56
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features Lab-leak / accidental release hypothesis

Recipients on this medium are inferred from channel membership, not per-message addressing.

I took the information from the channel on the SC2 spike mutations that arise on human-to-human passage and human-to-animal passage including serial passage in lab animals and put together this figure. First step was to make a Swiss model that fills in the gaps of the cryo structure. This is the complete sequence sans any disorderedregions or FCS mutations. It's striking that there are so many examples of the very same mutations in the UK/South Africa variants showing up during transfers to different species. Seems to me that the mutations fall into FIVE general classes, The ones that get the most attention and are likely key for interspecies transfer are of course the RBD mutations. There is strong evidence for immune selection in the RBD and in the N-terminal domain epitopes. The third hotspot for mutation is in and around the FCS. Whether or not this region is under immune selection isanyone's guess, but there is no doubt the region contributes to transmissibility. A fourth mutant class that is also likely to be under immune selection are what I've labeled the membrane proximal region [MPER]. There are some important MPER antibodies in HIV field, so these mutations could also be from immune selection. Finally, are the S2mutations, which group naturally with Doug. I suspect that these S2 mutations are likely not epitopes (but it's possible). Rather I think that Doug and A82V before it from EBOV are teaching that the adjacent mutation in two ofthe lions Q613R, plus other mutations that look to be mostly in the metastable regions of S2 could influencerefolding to the 6-helix bundle possibly affecting infection efficiency. Note - I'll change the human eventually tosomeone unlike @Covidfaker who actually was infected with SC2. [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
Seems to me that the mutations fall into FIVE general classes, The ones that get the most attention and are likely key for interspecies transfer are of course the RBD mutations.	quoted / not their view	quoted_external message body appears to be pasted content	asserts
There is strong evidence for immune selection in the RBD and in the N-terminal domain epitopes.	quoted / not their view	quoted_external message body appears to be pasted content	asserts

Statement

Grade

Attribution

Stance

Seems to me that the mutations fall into FIVE general classes, The ones that get the most attention and are likely key for interspecies transfer are of course the RBD mutations.

quoted / not their view

quoted_external message body appears to be pasted content

asserts

There is strong evidence for immune selection in the RBD and in the N-terminal domain epitopes.

quoted / not their view

quoted_external message body appears to be pasted content

asserts

In context

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

2020-12-30 14:56 Robert F. Garry

I took the information from the channel on the SC2 spike mutations that arise on human-to-human passage and human-to-animal passage including serial passage in lab animals and put together this figure. First step was to make a Swiss model that fills in the gaps of the cryo structure. This is the complete sequence sans any disorderedregions or FCS mutations. It's striking that there are so many examples of the very same mutations in the UK/South Africa variants showing up during transfers to different species. Seems to me that the mutations fall into FIVE general classes, The ones that get the most attention and are likely key for interspecies transfer are of course the RBD mutations. There is strong evidence for immune selection in the RBD and in the N-terminal domain epitopes. The third hotspot for mutation is in and around the FCS. Whether or not this region is under immune selection isanyone's guess, but there is no doubt the region contributes to transmissibility. A fourth mutant class that is also likely to be under immune selection are what I've labeled the membrane proximal region [MPER]. There are some important MPER antibodies in HIV field, so these mutations could also be from immune selection. Finally, are the S2mutations, which group naturally with Doug. I suspect that these S2 mutations are likely not epitopes (but it's possible). Rather I think that Doug and A82V before it from EBOV are teaching that the adjacent mutation in two ofthe lions Q613R, plus other mutations that look to be mostly in the metastable regions of S2 could influencerefolding to the 6-helix bundle possibly affecting infection efficiency. Note - I'll change the human eventually tosomeone unlike @Covidfaker who actually was infected with SC2. [shared file(s): image.png]
2020-12-30 15:09 Robert F. Garry open

Red spheres: the UK variant, Blue spheres: ZA variant, Magenta: both UK/ZA, Yellow spheres: animals.
2020-12-30 15:30 Andrew Rambaut open

Now if you had just produced that in time to be your Christmas card
2020-12-30 15:51 Edward C. Holmes open

Fantastic.
2020-12-30 15:52 Edward C. Holmes open

For the Christmas card I would replace the alpha helices with strings of face masks.

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