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sars-cov-2-variants / lineage-proposals

Repository to propose and discuss lineages
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MC.10.1 with S:S446N (6 seqs, 3 regions in Canada) #2172

Open Sinickle opened 2 days ago

Sinickle commented 2 days ago

GISAID query: C14757T,G16221T No. of seqs: 5 (4 from Saskatchewan, 1 from Ontario, 1 from Alberta) First: EPI_ISL_19446125, Saskatchewan Canada, September 8 Latest: EPI_ISL_19494753, Ontario Canada, October 9

Mutations relative to MC.10.1: Fair amount of synonymous. C10741T -> C10605T, C14757T -> G16221T, T18417C, G22899A, C25603T This only results in ORF1A:3447L, S:S446N

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Discussion: MC.10.1 with its additional S:A435S mutation appears to be one of the most fit variants today. This branch currently makes up 5/15 of sequences with S:S446N that have been submitted globally since July 1. Possibly the mutation is surviving on this lineage because MC.10.1 is very fit and therefore able to sustain detrimental mutations, or perhaps S:A435S has changed the favorability of S:S446N.

FedeGueli commented 2 days ago

Great catch Nick! Curiously 446N has been previously proposed in a XBF sublineage that was hard to die ! : https://github.com/cov-lineages/pango-designation/issues/2105

ryhisner commented 2 days ago

ORF1a:P3447L (NSP5_P184L), despite being C->T, is a rare mutation as well. Only ~70 sequences in 2024 have had it and fewer than 4000 ever. There's something interesting about the 175-185 range of NSP5, though I'm not sure what or why. I haven't read very much about NSP5, so I'm not sure where that region fits in the structure or what its role might be.

I don't know if S:K444N would be an advantageous mutation in KP.3 or not, but S446N makes it a possibility for the first time. Before, with G446S, K444N would've created a lethal glycan in the RBD. That option is now open in this branch.

FedeGueli commented 1 day ago

NSP5_P184L

@ryhisner if i am not wrong NSP5_Q189K is quite a strong mutation in conferring evasion from Paxlovid but i dont think 184 is involved.