Chat message

Slack / Private Message Drop, p.529 [SLACK_000743] · slack_pm:msg:05518

Date: 2021-02-20 08:06
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

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"So we have a common set of functional sites/effects for all the new variants: An RdRp mutation, an nsp6 modification, spike 613/614, some NTD mutations/deletions and some RBD mutations." *Incredible* examples of convergent evolution in real-time. The fact that this emerged in Uganda with not - to my knowledge - a massive number of cases is making me think perhaps that here at least individual adaptation for viral fitness in humans >immune escape. No NellY, EeeK, etc in the A.23.1 Uganda variant, which *may* be the better signs of immune escape *or* fitness plus immune escape.

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"So we have a common set of functional sites/effects for all the new variants: An RdRp mutation, an nsp6 modification, spike 613/614, some NTD mutations/deletions and some RBD mutations." Incredible examples of convergent evolution in real-time.	quoted / not their view	quoted_external inside quotation marks	asserts

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2021-02-20 07:36 Andrew Rambaut open

Bingo.
2021-02-20 07:39 Andrew Rambaut open

So we have a common set of functional sites/effects for all the new variants: An RdRp mutation, an nsp6 modification, spike 613/614, some NTD mutations/deletions and some RBD mutations.
2021-02-20 07:47 Robert F. Garry open

YES indeed! AS for the nsp6 mutations i'm betting functionally similar to the SGF del -the L98F mutations is probably the most important - in the same "external" loop as the SGF deletion and it makes WF more strongly aromatic. Tryptophans are not kept unless they are needed, so yes affecting regulation of whatever NSP6 is doingto interferon and/or autophagy. Not to dismiss the Met to Inosine mtations that are probably paired and doing something to that TM helix. [shared file(s): image.png]
2021-02-20 07:56 Robert F. Garry open

Thanks Andrew for the changes to the bat virological! Nicely done and overall much more focused and more importantly *effective* thanks to you and Eddie. @Kristian Andersen the bat-post looking good IMO. Let us know when you're able to take a brief look - life being insanely crazy all around.
2021-02-20 08:06 Robert F. Garry

"So we have a common set of functional sites/effects for all the new variants: An RdRp mutation, an nsp6 modification, spike 613/614, some NTD mutations/deletions and some RBD mutations." *Incredible* examples of convergent evolution in real-time. The fact that this emerged in Uganda with not - to my knowledge - a massive number of cases is making me think perhaps that here at least individual adaptation for viral fitness in humans >immune escape. No NellY, EeeK, etc in the A.23.1 Uganda variant, which *may* be the better signs of immune escape *or* fitness plus immune escape.
2021-02-20 08:07 Andrew Rambaut open

Will add ORF8 truncation/modification to that list.
2021-02-20 08:08 Andrew Rambaut open

@Robert Garry There is a cluster of A.23.1 that have Eeek in the UK (which is how I found it in the first place).
2021-02-20 08:10 Andrew Rambaut open

We are writing a paper about the B.1.1.7 variant including its origins and I would love to put some of this speculationin it and then perhaps lay it out in another paper. You interested in being involved? (any of you).
2021-02-20 08:19 Andrew Rambaut open

My current favourite hypothesis is that all of this is about increasing transmissibility in the face of global implementation of NPI which is why we have simultaneous explosive 2nd waves (Doug & Phil) and then the 3rd waves (VOCs). In particular I am wondering if partially-effective measures may have driven evolution for transmissibility in the same way that ineffective vaccines can. Doug & Phil arose in China during the first lock down period (but possibly outside of Wuhan in somewhere like Shanghai) but really took off in Italy. Displacedeverything globally except for areas like Africa where there was not much reported incidence and not much response and lineage A persisted. Then as incidence started to rocket, NPI were implemented and the lineage AVOCs were selected for.

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