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1. 2021-02-20 07:11 Andrew Rambaut open
   Interesting though is A.23.1 with Doug's neighbour Qeith. It has NSP12 Y346H - related?
2. 2021-02-20 07:12 Andrew Rambaut open
   (also 681R of course)
3. 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?
4. 2021-02-20 07:23 Andrew Rambaut
   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.
5. 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]
6. 2021-02-20 07:36 Andrew Rambaut open
   Bingo.
7. 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.
8. 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]

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