Slack / Private Message Drop — page 511

That nsp6 is cropping up a lot, isn't it. The B.1.525 I posted this morning has E484K and all three of the lineage defining B.1.1.7 deletions (plus Q677H - i.e. adjacent to FCS - possibly affects the O-linked glycs?). [2021-02-12 08:15:26] [Kristian Andersen] No coincidence that's for sure [2021-02-12 08:17:11] [Andrew Rambaut] No. We are working on a project trying to define the convergent peak for all this. I would love you all's input once we have put the guts together. [2021-02-12 08:22:14] [Kristian Andersen] It's definitely interesting - and I can't quite figure out what's going on here. Is it selection driving the same deletions? Or do we have some homology among these sites in general, and then during a chronic infection they're more likely to be cut out because of polymerase slippage, recombination, etc? When not deleted, how conserved are these sites in nucleotide space? Lots of interesting questions here - I definitely think they warrant a very close look since something is definitely going on. [2021-02-12 12:34:44] [Eddie Holmes] [thread - ID: 2021-02-12 12:34:44] https://www.washingtonpost.com/technology/2021/02/12/china-covid-misinformation-li-meng-yan/ "Even now, she is preparing another paper, nearing 30 pages, that she hopes will refute her critics and bring fresh attention to her claims about China, covid-19 and what she says is an international coverup campaign." That's us. [2021-02-12 12:35:03] [Robert Garry] A couple of factors from my corner. Most of the mutations are in loops (not beta sheets not helixes) which tend to be variable across all viral glycoproteins. The core amino acids the form a scaffold in virion (prefusion form) and postfusion forms that are more or less constant. The NTD and CTD also have a core structure that is more or less constant. Chronic infection is a rather special case as then immune selection/escape is going to play a more important role, if not the key role. Even a less "fit" virus might be selected under immune pressure if it can escape the immune response. However, transmission between two nonimmune humans is another thing. It's possible an immune escape could play a role (for ex: secretory IgA in respiratory secretions of the donor) but not clear. More likely for transmission it's mostly about virus loads or fitness to replicate in the URT. So a lot of mutations could impact that - ones that make the virus adsorb better (like in the NTD) or bind to receptors in the RBD better (NellY, EriK) or infect better P681H/R come to mind. But mutations in virus regulatory factors like NSP6 could also contribute. I'm actually a little surprised that there are not more transcriptase or other "run of the mill" replication competence mutations. The calculus for transmission changes again in humans with immunity - then it's likely to be more even mostly about immune escape, but you are not likely to select for less fit viruses in this case. [2021-02-12 12:40:25] [Robert Garry] [thread - ID: 2021-02-12 12:34:44] @Eddie Holmes One fact check: "Yan's paper on Zenodo -- despite several blistering scientific critiques and widespread news coverage of its alleged flaws -- now has been viewed more than *1 million times*, probably making it the most widely read research on the origins of the coronavirus pandemic, according to the Harvard misinformation researchers." *Only 1 M seems kinda paltry.* [2021-02-12 12:41:25] [Eddie Holmes] [thread - ID: 2021-02-12 12:34:44] @Eddie Holmes Not even close!