Slack / Private Message Drop — page 342

[Robert Garry] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195303/ From this modeling NSP6 looks like a viroporin to me - would have to look at the exact deletion, but most viroporins are involved in virion entry and cytopathogenesis. Same wheelhouse as the RBD and FCS mutations. [2020-12-23 05:21:04] [Robert Garry] Covs have other viroporins (E protein) that are virion associated, but NSP6 is likely remodeling cell membranes in some way to benefit virus replication. [2020-12-23 05:22:06] [Andrew Rambaut] Mmm. So definitely could be associated with a change in virus behaviour. Cool [2020-12-23 05:41:48] [Robert Garry] I'll map the deletion on the model, which is prob pretty accurate, when I get to the office after dropping off the dog. If it's in one of the loops would likely affect regulation and yes change virus behavior. [2020-12-23 05:45:05] [Andrew Rambaut] Seems to crop up with a small bunch in Australia with spike S477N, and a few others here and there. [2020-12-23 07:24:04] [Kristian Andersen] A lot of good stuff here Bob - thanks! And for Nelly, maybe we're too focused on spike alone... [2020-12-23 07:27:56] [Robert Garry] Right on cue - nonSpike protein nsp6 @Andrew Rambaut as predicted - the deletion is in a large external loop - very likely to impact nsp6 function or regulation! [2020-12-23 07:28:58] [Robert Garry] shared file(s): image.png [2020-12-23 07:36:34] [Robert Garry] TM domain 4 has the seemingly odd arginine. This is a sign of dimerization. That and the fact that the loop connects to this TM domain raises the suspicion these are part of the business/regulatory bits of the protein. [2020-12-23 07:48:48] [Robert Garry] AS for S477N - it would not surprise me to find that it's a contact residue with ACE2 - the ACE2 structures lack the n terminus (blue arrow) so plenty of opportunity for interactions. [2020-12-23 07:54:08] [Robert Garry] S477 [shared file(s): image.png] [2020-12-23 14:32:40] [Eddie Holmes] Brilliant work Bob! @Andrew Rambaut let we know about the Australian ones and I'll see what I can find out.