Slack / Private Message Drop — page 529

NSP12: Y346H Could the NSP6 have similar effects to the deletion? [2021-02-20 07:23:16] [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. [2021-02-20 07:33:49] [Robert Garry] Y346H -not directly in the groove itself *but right in line with the P323*. So putting that charged Histidine in is going to disrupt the bonding underlaying the channel and have a very similar effect to PhiL. [shared file(s): image.png] [2021-02-20 07:36:07] [Andrew Rambaut] Bingo. [2021-02-20 07:39:21] [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 07:47:29] [Robert Garry] 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 doing to 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 07:56:13] [Robert 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. [2021-02-20 08:06:52] [Robert Garry] [thread - ID: 2021-02-20 08:06:52] "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 08:07:41] [Andrew Rambaut] Will add ORF8 truncation/modification to that list. [2021-02-20 08:08:13] [Andrew Rambaut] [thread - ID: 2021-02-20 08:06:52] @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).