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Slack / Private Message Drop, pp.501-502 [SLACK_000715] · slack_pm:msg:05240

Date: 2021-02-09 07:15
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry

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SLACK_000716 The disulfides need to be broken in some case to allow S2 (HA2, GP2 etc) to refold to the 6 helix bundle - so you can get fusion peptides and the aromatic domain WPWYIWLGFIAGL in SC@ close together to mediate virus cell membrane fusion. [shared file(s): image.png]

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2021-02-09 06:54 Robert F. Garry open

Well Q613R showed up in the lion on the Christmas Card, so Q613H/R both adding positive charge. D614G takes away a negative charge. Something going on there for sure.
2021-02-09 07:10 Robert F. Garry open

Following Doug is a disulfide - Disulfide isomerases are important for virus entry - see references 28 and up in this paper.
2021-02-09 07:11 Robert F. Garry open

https://www.mdpi.com/1999-4915/13/1/53/htm
2021-02-09 07:15 Robert F. Garry

SLACK_000716 The disulfides need to be broken in some case to allow S2 (HA2, GP2 etc) to refold to the 6 helix bundle - so you can get fusion peptides and the aromatic domain WPWYIWLGFIAGL in SC@ close together to mediate virus cell membrane fusion. [shared file(s): image.png]
2021-02-09 07:15 Robert F. Garry open

Importantly you also need the protease cleavages to loosen up the structure disassociate the trimer so that the 6helix bundle can form and the fusion peptide (S) can interact with the cell membrane. REcall that in addition to the FCS there is also the S2' site with a putative fusion peptide right next door. So I don't see why ther couldn't beanother cleavage before the FCS with a fusion peptide here as well.
2021-02-09 07:15 Robert F. Garry open

So need to show that the elastase cleavage site is used but it's not out of the question and could make some sense. THere is a fusion peptide for sure between the FCS and S2' -looks like there may be one before the FCS as well.
2021-02-09 07:15 Robert F. Garry open

I still think that the most likely thing that Doug and the Q613H/R mutants are doing is adjusting the charge there andloosening up the trimer, but no reason that they couldn't be generating a new or better cleavage site as well.
2021-02-09 07:15 Robert F. Garry open

@Robert Garry Speaking of Cara's picture - She and Jonny both have them removed from the website - Jonny also scrubbed his weed research...

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