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Slack / Private Message Drop, pp.369-370 [SLACK_000583] · slack_pm:msg:03851

Date: 2021-01-09 07:02
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features

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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

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other https://journals.sagepub.com/doi/full/10.4137/BCI.S2049

Extracted statements

Rule-extracted, not adjudicated. The grade says what may be done with each one; read the document above before relying on any of them.

Statement	Grade	Attribution	Stance
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	own voice, substantive	speaker_own	asserts

Statement

Grade

Attribution

Stance

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

own voice, substantive

speaker_own

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

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

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 open

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.

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