XBB.2.3.3 Sublineage w/new S2' FCS—S:N450D, S:K478R, S:P812R, S:V1264L + 4x ORF1ab (6 countries, 48 seq, Jan 21)

[ryhisner]

Transferred from sars-cov-2-variants/lineage-proposals#656

Description

Sub-lineage of: XBB.2.3.3
Earliest sequence: 2023-7-30, Netherlands, Noord-Brabant — EPI_ISL_18098305
Most recent sequence: 2023-8-13, Netherlands, Noord-Holland — EPI_ISL_18115963
Countries circulating: Netherlands (2)
Number of Sequences: 2
GISAID AA Query: Spike_P812R, Spike_P521S
GISAID Nucleotide Query: G3620A, A6326G
CovSpectrum Query: Nextcladepangolineage:XBB.2.3.3* & S:P812R
Substitutions on top of XBB.2.3.3:
Spike: N450D, K478R, P812R, V1264L
ORF1a: T224I, G1119S, T2021A
ORF1b: G977C
Nucleotide: C936T, G3620A, A6326G, A13021G, C15540T, G16396T, A17622G, A22910G, A22995G, T23830C, C23997G, G25352C, C26936T

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/XBB.2.3.3_N450D_K478R_P812R_V1264L.json?c=gt-S_812&gmax=25384&gmin=21563&label=id:node_4102599

Evidence
XBB.2.3* lineages has curiously been much slower than XBB.1*+S:S486P lineages to pick up advantageous spike mutations, particularly S:F456L (in 0.69% of XBB.2.3* in the past 3 months compared to 18.7% of XBB.1*+S:F486P) and L455F-F456L (1067 sequences of XBB.1*+S:F486P w/Flip compared to zero XBB.2.3*). S:N450D has been extremely rare in both, however, appearing in just 51 sequences in the past three months.

But the most interesting aspect of this 2-sequence (so far) saltation branch of XBB.2.3.3 is the presence of S:P812R, which @thomaspeacock informed us creates a new furin-cleavage site (FCS) at the S2' location. See his explanation at Pango Github issue #1627 here: https://github.com/cov-lineages/pango-designation/issues/1627 .

This lineage also has S:K478R, which has proven to confer a growth advantage in XBB lineages, and S:V1264L, which has proven to be an advantageous mutation in the past, and which has a solid fitness advantage according to the Bloom Lab amino-acid fitness calculator.

Genomes

Genomes

EPI_ISL_18098305, EPI_ISL_18115963, EPI_ISL_18130456, EPI_ISL_18136960, EPI_ISL_18136963, EPI_ISL_18286700, EPI_ISL_18299958, EPI_ISL_18331374, EPI_ISL_18392989, EPI_ISL_18393096, EPI_ISL_18393098, EPI_ISL_18398856, EPI_ISL_18398858, EPI_ISL_18403515, EPI_ISL_18403933, EPI_ISL_18419955, EPI_ISL_18421656, EPI_ISL_18441622, EPI_ISL_18444758, EPI_ISL_18444761-18444762, EPI_ISL_18444840, EPI_ISL_18446173, EPI_ISL_18467510-18467513, EPI_ISL_18467516-18467517, EPI_ISL_18467525, EPI_ISL_18467588, EPI_ISL_18471202, EPI_ISL_18520168, EPI_ISL_18535805, EPI_ISL_18536101, EPI_ISL_18584927, EPI_ISL_18584952, EPI_ISL_18640365, EPI_ISL_18674275, EPI_ISL_18674905, EPI_ISL_18674917, EPI_ISL_18694629, EPI_ISL_18701935, EPI_ISL_18712638, EPI_ISL_18754699, EPI_ISL_18754879, EPI_ISL_18763381,

[FedeGueli]

thanks