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Slack / Private Message Drop, pp.23-24 [SLACK_000237] · slack_pm:msg:00235

Date: 2020-05-12 21:28
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen

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> My first look at the virus suggested that the pattern of distribution of sequence variation across the genome looked natural, but that may too broad brushAny new evidence on this? I haven't looked at e.g., dN/dS for a while.

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2020-05-12 21:22 Kristian G. Andersen open

Initially we thought the O-linked glycans could somewhat rule out lab culture (or wouldn't be consistent with), but I'm much less sure now - I'm not convinced they actually form a glycan shield and instead may help regulate the site itself. The low dN/dS value - primarily in the spike - has always been peculiar to me and a tiny bit suggestive ofculturing.
2020-05-12 21:24 Edward C. Holmes open

Thanks. Very important.
2020-05-12 21:25 Edward C. Holmes open

My first look at the virus suggested that the pattern of distribution of sequence variation across the genome looked natural, but that may too broad brush.
2020-05-12 21:28 Kristian G. Andersen open

The three main new things that bothers me - the first two shown in this post http://virological.org/t/identification-of-a-common-deletion-in-the-spike-protein-of-sars-cov-2/451: 1. The furin site is clearly active in tissue culture. We see the virus lose it under some culturing conditions, but this effect could be very cell-type specific. What bothers me here is that the virus is clearly fiddling with this site inculture. If it can lose it, likely it can gain it? Typically SARS-like CoVs are cultured in the presence of trypsin (to allow for cleavage of S1/S2), but if trypsin isn't added, there's a *huge* selection pressure for gaining a furin site. SARS-CoV-2 can grow without trypsin - other SARS-like CoVs can't.2. The example from bovine CoVs (post #6 on the thread on virological) is exactly a 12bp insertion seen in tissue culture creating a furin cleavage site.3. We have now seen multiple examples of SARS-CoV-2 de novo obtaining exactly 12bp insertions in different partsof the spike, but only in tissue culture. They're not furin sites, but there seems to be some affinity specifically for12bp insertions (in T/C) - and of course, the furin cleavage site is exactly 12bp. There could be some specific mechanism behind this. We're looking into this a little closer at the moment.
2020-05-12 21:28 Kristian G. Andersen

> My first look at the virus suggested that the pattern of distribution of sequence variation across the genome looked natural, but that may too broad brushAny new evidence on this? I haven't looked at e.g., dN/dS for a while.
2020-05-12 21:29 Edward C. Holmes open

Got it. No new evidence.

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