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Slack / Private Message Drop, p.711 [SLACK_000925] · slack_pm:msg:07461

Date: 2021-04-16 11:23
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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It's the corridor that was discussed above. PhiL and DouG (or similar mutations) open a door and the virus walksdown to improve infection of humans. So the corridor involves: NTD front face: e.g. E154K (Eek, Jr?) or others, oneor couple of RBD mutants (enhanced binding/immune escape) and a FCS enhancing mutation. Throw in the nsp6 loop deletion or another mutation near and you've got amore efficient virus.

In context

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2021-04-16 11:05 Kristian G. Andersen open

@Robert Garry - thoughts on some of these mutations in the "Indian" B.1.617 variant? The three spike mutations at154, 452, and 484 certainly appear immune related. [shared file(s): Screen Shot 2021-04-16 at 11.04.11 AM.png]
2021-04-16 11:12 Kristian G. Andersen open

Interestingly, B.1.617 doesn't have the deletion in ORF1a, but it has a mutation very close by - I wonder if it might behaving the same effect.https://outbreak.info/compare-lineages?pango=B.1.1.7&pango=B.1.351&pango=P.1&pango=[...]pango=B.1.617&gene=ORF3a&gene=N&gene=ORF1a&gene=S&threshold=75 [shared file(s): Screen Shot 2021-04-16 at 11.10.13 AM.png]
2021-04-16 11:23 Robert F. Garry

It's the corridor that was discussed above. PhiL and DouG (or similar mutations) open a door and the virus walksdown to improve infection of humans. So the corridor involves: NTD front face: e.g. E154K (Eek, Jr?) or others, oneor couple of RBD mutants (enhanced binding/immune escape) and a FCS enhancing mutation. Throw in the nsp6 loop deletion or another mutation near and you've got amore efficient virus.
2021-04-16 11:26 Kristian G. Andersen open

Eek, Jr - love it :wink:. the del3675/77 is the nsp6 deletion, correct?
2021-04-16 11:31 Robert F. Garry open

I think that's correct. Also, the nonbat "mutations in" Spike (A372 - knocks out a glycosylation site and H519) likely give SC2 a leg up - ie maybe makes it more pan-tropic. Of course need to mention the PRRA nonbat insertion too.
2021-04-16 11:39 Robert F. Garry open

I think this is the NSP6 mutation in B.1.617 [shared file(s): image.png]
2021-04-16 11:48 Kristian G. Andersen open

Which one in that figure?

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