KP.3.1.1 +ORF1b:S1658Y +ORF9b:P39L branch acquired S:W64C, ORF1a:N4351T (16 seq, 4 countries)

[ryhisner]

Description Sub-lineage of: KP.3.1.1 Earliest sequence: 2024-6-2, Spain – EPI_ISL_19225587 Most recent sequence: 2024-8-2, USA, New York – EPI_ISL_19341409 Continents circulating: Europe (6), North America (4) Countries circulating: USA (4), Spain (3), France (1—travel to USA), Ireland (1) Number of Sequences: 9 GISAID Nucleotide Query: A13209C, G21754T CovSpectrum Query: Nextcladepangolineage:KP.3.1* & [2-of: A13209C, C19572T, G21754T] Substitutions on top of KP.3.1.1: Spike: W64C ORF1a: N4315T (NSP10_N62T) Nucleotide: A13209C, C18440A, C19572T, G21754T, C28399T

Phylogenetic Order of Mutations: C18440A (ORF1b:S1658Y) → C28399T (ORF9b:P39L edited) → A13209C, C19572T, G21754T (ORF1a:N4315T, S:W64C)

USHER Tree https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/KP.3.1.1_W64C_N4315T.json?c=gt-S_64&gmax=25384&gmin=21563&label=id:node_7032655

Evidence This is probably not a very fast lineage, but I find it interesting for other reasons.

So far, S:S31del has been mostly incompatible with mutations in the S:58-65 range, though they’ve been very popular in non-S31del lineages. In the BA.2 spike structure (there is no structure in this region for BA.2.86 that I know of) S:20-33 and S:58-67 run anti-parallel to each other, practically entangled. Maybe addition of a glycan at N30 causes some sort of steric hindrance that prevents the common S:58-65 mutations (mainly F58L, F59S, F59L, S60P, W64R I think) from occurring. But perhaps the location and the fact that W→C involves a change from a very bulky AA to a much smaller AA makes this mutation permittable. Unlike all the others, this one requires a transversion mutation (G→T) that’s less common than the transitions that lead to the other, so perhaps that’s why it hasn’t appeared as often.

Then again, unpaired cysteines tend to be destabilizing, so this may well be a deleterious mutation.

Lastly, it seems likely that the ORF1a:S4286C/NSP10_S33C mutation of KP.3.1.1 is at least slightly deleterious. Perhaps ORF1a:N4315T/NSP10_N62T is compensatory?

Genomes

Genomes

EPI_ISL_19225587, EPI_ISL_19280658, EPI_ISL_19289809, EPI_ISL_19293739, EPI_ISL_19320548, EPI_ISL_19323178, EPI_ISL_19341296, EPI_ISL_19341394, EPI_ISL_19341409,

[FedeGueli]

the parental branch has also ORF9b:P39L (C28399T)

[FedeGueli]

12 with two new US states

[FedeGueli]

13 , last from TX.

But interestingly it seems to have gained further S:S155I in two sequences, one of them with S:P486S not sure if real

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice4_genome_test_231d9_bbe330.json?label=id:node_7040136

[FedeGueli]

+1