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1. 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]
2. 2021-02-20 07:36 Andrew Rambaut open
   Bingo.
3. 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.
4. 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]
5. 2021-02-20 07:56 Robert F. Garry
   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.
6. 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.
7. 2021-02-20 08:07 Andrew Rambaut open
   Will add ORF8 truncation/modification to that list.
8. 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).
9. 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).

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