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Slack / Private Message Drop, p.529 [SLACK_000743] · slack_pm:msg:05515

Date: 2021-02-20 07:39
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut
Topics: Furin cleavage site and molecular features

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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.

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Statement	Grade	Attribution	Stance
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.	own voice, substantive	speaker_own	asserts

Statement

Grade

Attribution

Stance

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.

own voice, substantive

speaker_own

asserts

In context

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2021-02-20 07:14 Andrew Rambaut open

Full complement is: Spike: F157L, V367F, Q613H, P681R, R102I N: Q39R, S202N NS8: L84S, E92K NSP4: T495I NSP6: L98F, M183I, M86I NSP12: Y346H Could the NSP6 have similar effects to the deletion?
2021-02-20 07:23 Andrew Rambaut open

Much of this is discussed in https://www.medrxiv.org/content/10.1101/2021.02.08.21251393v1.full.pdf but I don't think we mentioned the RdRp mutation because P323L has never really been talked about yet.
2021-02-20 07:33 Robert F. Garry open

Y346H -not directly in the groove itself *but right in line with the P323*. So putting that charged Histidine in is goingto disrupt the bonding underlaying the channel and have a very similar effect to PhiL. [shared file(s): image.png]
2021-02-20 07:36 Andrew Rambaut open

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

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 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." *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.

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