Private channel session 573
18 messages over 58m, 2020-11-17 – 2020-11-17.
A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.
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What a dick move from Frankie Bollocks... Good for you calling him out @Andrew Rambaut!
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One thing from the preprint I agree about though - and mentioned when I testified in front of the Danish parlamentyesterday "The rapid acquisition and spread of SARS-CoV-2 mutations in minks suggests that if a similarphenomenon of host adaptation had occurred upon its jump into humans, those human-specific mutations would likely have reached fixation already before the first SARS-CoV-2 genomes were generated". That could very likelybe true - ultra fast fixation during the first few rounds of human to human transmission.
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Yes. I have been saying that for years. Clear in avian flu too (the same mutations come up). Adaptations to the within-host environment are very rapid. Adaptations to transmission will be much slower. Thus viruses that jump and spread are likely already able to spread but may need some tweaking for within-host growth.
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The other thing that virologists struggle with is that better receptor binding does not equal fitter viruses.
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But even with the mink, there are lots of lineages in Marion's trees that don't have Y453F.
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Yup, I have been hearing you saying this for years - for Ebola too. For SARS we actually got to see some of those mutations because we captured the intermediate host - would be very interesting to see for SARS2 as well, but the mink data is definitely interesting in this regard.
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Yeah, I'm not quite sure what Y453F is about - might just be marginally beneficial.
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It appears sufficient times in mink to mean it must be selected for but possibly quite weakly. And possibly as a resultof the high density.
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Yup - plausibly this one becomes fixed when big populations get hit. A lot of diversity in the size of the various farms- especially in Denmark (not sure about NL - but I think they have more 'mega' farms).
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Here is a report I wrote for the WHO. To me the most interesting thing is the spike deletion at 69/70 that appears after Y453F and also appears after N469K in humans [shared file(s): Mink-associated_mutations_in_humans.pdf]
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Note also the Utah human - also mink related, also 453F (slightly confidentially).
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One thing to be a data parasite (which implies some relationship to the host) and a data thug/thief.
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Thanks Andrew for sharing - very interested to get your insights into this. Will keep confidential - A LOT of disagreement in DK about how to handle that (most of those discussions driven by people that have no background in any of this...).
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We (WHO working group) did talk to the SSI but they were very cagy (as you might expect). But they sharing isolates now through the WHO I believe.
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FWIW - the 69/70 S deletion comes at a region that is disordered at least in some spike structures (reddish sphereshere). It's at the top of the spike but not close by to Y453 (bluish) so not obvious why the might be linked. Not likesubstructures that interact (for example the 6 helix bundles) where you expect compensatory/complementarymutations. [shared file(s): image.png]
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> We (WHO working group) did talk to the SSI but they were very cagy (as you might expect). But they sharing isolates now through the WHO I believe. Yup, no surprise there - unfortunately. And yes - I believe they have shared the isolates widely now (including withUS) labs, so hopefully we'll learn more soon. I think they got a little surprised by how strongly the scientific community pushed back at them for not releasing data, so hopefully they have learned a lesson. (unfortunately way too much focus has been put on the mistakes here though - it's really important we remember that the main issue here is a parallel (raging) epidemic in mink).
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Some wild speculation if you want to "connect" 69/70 to 453. MERS-CoV uses both [either?] a protein and a sialicacid receptor. HKU1 uses sialic acid and of course SARS CoVs use ACE2. What's not known [here's the speculation] is if the NTD of SARS-CoV2 (where the 69/70 deletion is actually part of a receptor binding domain forsialic acid or other molecule. If so a deletion in the NTD affecting binding to this receptor might affect entry driven bythe CTD. Receptor swapping is definitely a thing in HIV (chemokine receptors). [shared file(s): image.png]
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and now @Kristian Andersen i'll get back to my project1 report