Private channel session 1654
47 messages over 2h 9m, 2021-11-24 – 2021-11-24.
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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This variant is completely insane - https://github.com/cov-lineages/pango-designation/issues/343
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Mutating itself to death, indeed
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Check this bit... [shared file(s): image.png]
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And a bit of FCS adjacent action... [shared file(s): image.png]
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Plus 69/70 del and the nsp6 del
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Holy shit - that is quite something. The length of that branch... :scream:. What's the N/S on the branch?
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Just had a look at the list of mutations - so nuts. Getting rid of a lot of serines (although also adding some new ones...) and adding in lysine - the friggin' genome is going to be made out of lysines at some point! Just nuts.
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Oh boy - it's getting more polybasic - that's not good....
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It must surely be from a immunocompromised chronic infection. Possibly a dual infection with recombination and heavy mutation. But the random traveller in HK has me very worried
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Visited South Africa for 20 days - must be a much more prevalent virus than the sequencing suggests
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Will cause S gene dropout and I think SA is seeing some signal of that apparently
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HIV patient or animal reservoir - I'll say 70/30 odds.
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Bob, presumably the N679K combined with P681H makes this a better FCS, correct? It's interesting to see E484A inthere too - presumably E484K was a bit too much.
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I swear to god - if we see another monster variant gain territory here in November/December, something is driving the emergence. What, I don't know, but "something".
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Yes definitely better FCS - the RXXR site really is minimal. Any changes that put postive charges, K, R, H nearbyare going to up the efficacy. It already as discussed has an effective furin landing site in QTQT
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LPAI goes from a minimal site to multiple basic residues in HPAI... [shared file(s): image.png]
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Yup. QTQT is a landing site?
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yes both are neutral polar animo acids
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I assume you say it cutie-cutie?
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I had missed that previously, but that's actually kinda interesting - because: [shared file(s): furin_aa_nov21.png]
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For the non-SC2 viruses they _either_ have QTQT _or_ the indel - but not both. SC2 has both.
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The RmYN02-like are quite distant to SC2 in this bit of the genome. Is it not more interesting that RaTG13/BANAL-20-52-like viruses acquired the QTQT motif?
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Yup - almost looks step-wise.
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Indeed - that's always puzzled me.
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What would it do without the PRRA insert?
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I've think that the enzymes that do the cleavage at R/S also probably benefit by having a "landing pad."
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So if you were going to pick a virus from amongst your large bank of samples in which to try popping a FCS insertion you would pick out one with QTQT?
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Not without having all the knowledge in hindsight.
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Fair enough. I won't tweet that then.
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Same argument with the O-linked glycans - without having SC2 as the guidepost - you would not know....
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Good - that would just encourage the Leakers...
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Yeah, very clearly not a conscious choice - just nature doing it's thing. All it took was a virus with a landing site and then stuff comes and goes around that site all the time - just had to be the right sequence that popped in.
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Yup - nature - we get to see the brilliance but only afterwards.
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Some alignments with these sequences combined with relevant SARSr-CoVs - just FYI. [shared file(s): 2021.11.24_alignment_spike_nt.geneious, 2021.11.24_alignment_spike_aa.geneious, 2021.11.24_alignment_spike_aa_minimal_annotated.geneious]
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This is mind blowing - BANAL-52 is closer to Hu-1 in the spike (in AA space) than the Botswana sequences are.... Holy fuck.
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98.4% vs 96.9%
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Yeah - what I really want to do is put the PRRA into BANAL-52 and see how it does several species.
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What the heck is up here - Hu1 on top, Botswana at the bottom [shared file(s): Screen Shot 2021-11-24 at 9.07.10AM.png]
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In AA space: [shared file(s): Screen Shot 2021-11-24 at 9.07.32 AM.png]
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Here's the key part of the RBD - contact residues listed in purple above. This makes me believe this could be evolution in a non-human host, so I'll have to change my 70/30 odds to 50/50 based on this alone. This is very interesting. [shared file(s): Screen Shot 2021-11-24 at 9.08.55 AM.png]
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Agree - it's freaky!
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The insertion ("TAGTGCGTGAGCCAGAA") around 630 could be interesting - obviously a short sequence, but it ain't from SC2 itself and the top BLAST results match fungi, cholera, and a fish...
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THis insertions are rare - wasn't there a preprint or virological post on those a while back?
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Yeah - same Tom: https://virological.org/t/putative-host-origins-of-rna-insertions-in-sars-cov-2-genomes/761
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@Andrew Rambaut But saying it out loud only can get you in deep trouble.
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Yes - Tom has identified that insertion in a human mRNA
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Somewhere on twitter