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sars-cov-2-variants / lineage-proposals

Repository to propose and discuss lineages
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BQ.1.1 saltation with S:Y144del, H245Y, N343S, N417D, A653V and 15+ additional non-spike aa mutations (2 seqs, US) #1528

Closed Vnes97 closed 3 months ago

Vnes97 commented 5 months ago

Sequences: EPI_ISL_19036878, PP713005.1 (Likely from the same patient, though metadata indicates that it is sequenced from baseline surveillance). BQ.1.1 recently (March 21st 2024) sampled with interesting mutation profile. Earliest sequence: 21.03.2024 (United States) Countries detected: United States aa mutations: BQ.1.1+ ORF1a: F8L (2-nuc), I114V, V627I, S1272N, S1372A, K2507R, S2972P, T2977I, I4098T ORF1b: V87I, V1164M, P1570S, Q2635H S: Y144del, H245Y, N343S, N417D (2-nuc), A653V E: I9T M: L67F, H125Y ORF7a: T115I Though BA.5 descendents tend to have low Spike mutation rate than other Omicron sublineage in chronic cases, this BQ.1.1 has some rare mutations such as S:N417D that needs to be monitored. The 2-nuc mutation ORF1a:F8L in ORF1a's signal peptide is also worth notifying. Gisaid query: T287C, C289A, G22599C EDIT: one of them (PP713005.1) has an additional ORF1a:V366I

Vnes97 commented 5 months ago

This one seems to trade ACE2 binding for immune escape, but with little success image

FedeGueli commented 5 months ago

S:N343S removes the key N Glycan at 343. I think @ryhisner found this one too.

ryhisner commented 5 months ago

Anything that removes the N343 glycan has to involve a serious rearrangement of spike, so I don't know how accurate current ACE2 affinity or antibody-evasion assays will be. M:H125Y is a classic chronic mutation that Tom Peacock first identified in an analysis of immunocompromised patients.

The E:I9T reversion is a fascinating one. It's occurred dozens of times, almost always in exceptionally divergent chronic-infection sequences. There have been various claims made about E:T9I, but I'm not sure I believe most of them as I think they're all overexpression studies.

ryhisner commented 5 months ago

Another interesting aspect of this one is the 2-nuc ORF1a:F8L, which had to have been acquired via recombination with the TRS-L. It seems that it has only been in about 25 sequences ever.

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FedeGueli commented 4 months ago

Thanks @ryhisner !

FedeGueli commented 4 months ago

No new sequence of this i m closing it