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Slack / Private Message Drop, p.548 [SLACK_000762] · slack_pm:msg:05717

Date: 2021-02-25 07:57
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen

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I'm talking to Charles later this morning btw - I think he got a little spooked and is realizing that maybe his data isshit... I think the potential transmission advantage of the variant is interesting, so worth looking at that further - but not the way Charles did. Won't matter in a few weeks though - B.1.1.7 is going in for the knockout.

In context

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2021-02-25 07:51 Robert F. Garry open

B.1.427 and B.1.429 Charles loves the spotlight - has ever since the "heady" days of Bas-Congo Virus. But what really got me intrigued is the W152C mutation. An unpaired cysteine - not likely to be selected for or even tolerated.WTF is a common theme with this virus. So digging into this a bit I have a "theory." The cysteine could be creating ametal chelating spot. SEE FIGURE. Also check back above the two"new cysteines in the Weifeng alignment in theHA321 Rhinolophus stheno, HA363 Rhinolophus malayanus, HA442 Rhinolophus malayanus viruses - same spot inthe NTD so these could form a new metal chelating spot with two of the histidines as well [equally likely a newdicysteine loop]. Finally the two new cysteines that popped up in @Kristian Andersen "reinfection" patient could alsobe doing the metal chelation thing with the histidines or forming their own new dicysteine loop. [shared file(s): image.png]
2021-02-25 07:52 Robert F. Garry open

Someone with a cyroEM really needs to take a look.
2021-02-25 07:55 Kristian G. Andersen open

Interesting... Hasn't it previously been hypothesized that the FCS itself is involved in metal chelation, potentiallyexpanded the receptor usage of the virus? That site is pretty interesting- we also see R and L in that position at times:https://nextstrain.org/ncov/global?c=gt-S_152
2021-02-25 07:57 Kristian G. Andersen

I'm talking to Charles later this morning btw - I think he got a little spooked and is realizing that maybe his data isshit... I think the potential transmission advantage of the variant is interesting, so worth looking at that further - but not the way Charles did. Won't matter in a few weeks though - B.1.1.7 is going in for the knockout.
2021-02-25 08:04 Robert F. Garry open

@Kristian Andersen Heparin sulfate binding I think.
2021-02-25 08:37 Kristian G. Andersen open

Charles actually looked at binding of W152C in his 'paper'. Decreased binding - by quite a bit (manu above). [shared file(s): Screen Shot 2021-02-25 at 08.36.44.png]
2021-02-25 08:52 Kristian G. Andersen open

@Andrew Rambaut - I assume this isn't actually a pango issue, right? [shared file(s): Screen Shot 2021-02-25 at 08.51.50.png]
2021-02-25 09:10 Andrew Rambaut open

This was happening occasionally - a false positive P.1. probably due to convergence. We have fixed this now in the latest pangolin so P.1s will only be called based on having 5 or more of the defining mutations.

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