Private channel session 1606
30 messages over 1h 10m, 2021-09-14 – 2021-09-14.
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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So, the Proline at 681 is important for the O-glycans. S at 681 changes the prediction from three to only one O-linked glycan - as @Kristian Andersen has pointed out this likely is involved in regulation of cleavage - rather than any "glycan shielding." [shared file(s): image.png]
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Interestingly this is actually a R681S mutation
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(i.e., a Delta)
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Of course N501 is the a key residue for cross-species transmission. N501T is a key mutation for minks and ferrets. Serine is chemically similar to Threonine.
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Mutation of two amino acids (K479N and S487T) in palm civet SARS-CoV RBD allows this virus to infect humans (Li, 2008). These changes overcome the species barrier between civets and humans and enable favorable interactions between the RBD and contact residues on human ACE2. Q493 and N501 are the two SARS-CoV-2 residues that have similar interactions with ACE2 as SARS-CoV residues N479 and T487.
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R681S - That is interesting - hard to predict the effect on cleavage. The fsc is still there of course, but cleavage could be improved (the S might be a better landing site than the R) or decreased. And, the wild-card of the O-glycans not being there.
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These are the mutations we are seeing (we are not sure how they are linked as they are environmental samples). The last column is me looking outside the SARS-CoV-2 to the bats/pangolins ```S:R102T (21867:G>C) conserved S:D442N (22886:G>A) conserved S:Y449H (22907:T>C) 449F 449G S:N450T (22911:A>C) 450S (RaTG13), 450G S:P499S (23057:C>T) 499S (Cambodian bats) S:N501D (23063:A>G) 501D (RaTG13), 501T, 501V S:N501S (23064:A>G) S:Q506P (23079:A>C) conserved S:P681S (23603:C>T) missing S:V772A (23877:T>C) conserved S:Q779L (23898:A>T) conserved S:L828I (24044:C>A) conserved S:G932D (24357:G>A) conserved S:S937A (24371:T>G) conserved```
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question is - does any of this spike profile make you think it might be in a non-human host?
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501D is interesting as it is in RaTG13 (i.e., one of the residues SC2 ancestors lost)
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For completeness - here's P681R - as discussed previously it changes one of the O-linked glycans [shared file(s): image.png]
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The loss of furin cleavage and some RBD mutations seems like it might be non-human
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There are about 100 681S human genomes on GISAID and some evidence of transmission clusters so can't be a totally unfit virus in humans
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THe FCS will still be there but most likely not as good as P681R. Totally agree about the N501 S or D maybe non-human. That could be spillback followed I guess by another spillover..
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That is a weirdly mutates spike... Often we see charge reversions, but that's not what's going on here - instead we see several hydroxyl groups? There are more S/T mutations in that spike than the two you mentioned. Novel receptor?
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This is highly confidential right now but it is from wastewater in a city. It has been frequently coming up over time and has not been seen in any of the human cases in the city (and as you know we do sequence a lot). We are speculating it is in rats or something.
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The good news is probably that this will be less fit in humans and is not a particular threat (above Delta which wealready have). Would be interesting though.
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Very interesting!
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Indeed - that is interesting. As you say, could likely be animals, but yes, probably not a concern in humans compared to delta.
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Don't rodent CoVs have funky FCSs? Question for Stephen...
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SLACK_001212 MHV changes its FCS all the time
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See here - no making fun of my tree. [shared file(s): image.png]
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Got another FOIA from ae: will be declined again and probably end up in court again. This is what my Uni told me (apparently the Uni cyber security people have kindly collated all my emails for me):
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And for context, the application was another from Ea. Associated Press. The final scope of the application is: _AIl University of Sydney email correspondence between personnel of the University's Viral Evolution Lab and:_ Anthony Fauci (email address afauci@niaid.nih.gov, AF10r@nih.gov)__ Kristian Anderson (email address Marion Koopmans (email address Andrew Rambaut (email addres: Jeremy Farrar (email address Collins Francis (email address trancis.collins@n Gontaining the search terms "Phytogenic", "coronavirus' to 15 June 2020. uk)_ jov)_ "Wuhan", and "GISAID" for the period 15 December 2019
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I can confidently predict that the number of emails containing the words - "Phytogenic'", "coronavirus", "Wuhan", _and_ "GISAID" is zero.
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Ignoring the spelling of 'phytogenic' this is amateur stuff - what useless keywords.
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Apparently my Uni people corrected 'phytogenic' to 'phylogenetic'
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When they say 'and' do they actually mean 'or'?
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I guess or.
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Going back to this channel for this but this stuff about the DARPA proposal makes me even more angry about the DT letter (if it is indeed Baric) - he knew how suspicious a FCS would look back then.
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And his attacks on me for even suggesting we needed to take a look at this. He's a two-faced bastard, that's for sure.