Slack / Private Message Drop — page 370

Just a reminder [to self] that in terms of Eeek and Pooh :clap: E484K is very likely a product of immune escape at some point in the transmission chain - one if if not the dominant neutralizing epitope. It does not appear to interact with ACE2 directly [but all protein structures are models and all models are wrong]. Pooh - deserves a second:wave: round - appears to be an upgrade at the FCS. As the paper cited below summarizes the FCS is actually influenced a lot by the flanking residues on either side. H being a positive charge in the P5 position is an upgrade to the furin site from P. https://journals.sagepub.com/doi/full/10.4137/BCI.S2049 [2021-01-09 07:06:55] [Robert Garry] Also worth noting that the upstream residues QTQTN that Andrew et al and others have shown are often deleted in cell culture (SC2 doesn't need a FCS in culture apparently) are pretty much a PERFECT upstream context sequence for optimal FCS cleavage being small and hydrophilic amino acids. @Kristian Andersen maybe Karthik could look but I think this deletion or something like it showed up as a minor species showed up in the Vero passage that Brandon did. QTQTN is present in GD pangolin and RaTG13, but not SC1. [2021-01-09 07:25:56] [Andrew Rambaut] We have also seen an odd import (possibly from Uganda - but quite possibly with an intermediate location) that has P681R so making the FCS RRRK - any thoughts on that? Interestingly it also has V367F & Q613H (but not 614G - it is in lineage A). A small cluster, possibly growing. [2021-01-09 07:39:57] [Robert Garry] Interesting - P681R would make the FCS RRRAR right? which is predicted to be a much better site than PRRAR but not as good as RRAR/KR. Q613H is pretty analogous to the lion mutation (from my virological christmas card) Q613R, both to a positive charge at pH >6. [2021-01-09 07:42:04] [Andrew Rambaut] There are lions in Uganda. [2021-01-09 07:42:23] [Andrew Rambaut] (so I have heard - I was supposed to be going there last year, sigh) [2021-01-09 07:52:11] [Robert Garry] Ahhh yes - the Queen Victoria hotel is pretty special and you can take a side trip to the Ziika forest. Curious about Pooh, showing up in NIgeria (Christian Happi) and now Poor in Uganda. Not that many sequences from Africa, Something usual in Africans going on which I suspect relates to prior exposure to some yet uncharacterized betacornaviruses. [2021-01-09 07:54:30] [Robert Garry] Lot of immunosuppressed Africans, HIV and other causes, as well. So having the P681 changes may fit that meme. [2021-01-09 08:00:28] [Andrew Rambaut] This is the new USA cluster with Eeek and Pooh: [shared file(s): image.png] [2021-01-09 08:11:00] [Robert Garry] [thread - ID: 2021-01-09 08:11:00] All in Maryland? Worth keeping an eye on it for sure... [2021-01-09 08:12:37] [Andrew Rambaut]