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Slack / Private Message Drop, p.370 [SLACK_000584] · slack_pm:msg:03853

Date: 2021-01-09 07:25
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut

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We have also seen an odd import (possibly from Uganda - but quite possibly with an intermediate location) that hasP681R so making the FCS RRRK - any thoughts on that? Interestingly it also has V367F & Q613H (but not614G - it is in lineage A). A small cluster, possibly growing.

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2021-01-09 06:35 Robert F. Garry open

Interesting (from Hopkins -sidenote daughter whose finishing up her doctorate there just got the second dose of Phizer - fever muscle aches not pleasant).
2021-01-09 07:02 Robert F. Garry open

Just a reminder [to self] that in terms of Eeek and Pooh :clap: E484K is very likely a product of immune escape atsome 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 alot 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 Robert F. Garry open

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 Andrew Rambaut

We have also seen an odd import (possibly from Uganda - but quite possibly with an intermediate location) that hasP681R so making the FCS RRRK - any thoughts on that? Interestingly it also has V367F & Q613H (but not614G - it is in lineage A). A small cluster, possibly growing.
2021-01-09 07:39 Robert F. Garry open

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 Andrew Rambaut open

There are lions in Uganda.
2021-01-09 07:42 Andrew Rambaut open

(so I have heard - I was supposed to be going there last year, sigh)
2021-01-09 07:52 Robert F. Garry open

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 uncharacterizedbetacornaviruses.

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