CH.1.1 Sublineage with S:T299I, S:R403K, S:D1165G, ORF10:I4V (19 seq, Mar 24)

[ryhisner]

Description

Sub-lineage of: CH.1.1
Earliest sequence: 2023-1-26, England — England/DHSC-CYGDD31/2023 (not on GISAID)
Most recent sequence: 2023-2-28, England — EPI_ISL_17105228
Countries circulating: England (16)
Number of Sequences: 16
GISAID AA Query: Spike_R403K, Spike_T299I, Spike_D1165G
GISAID Nucleotide Query: G2357A, C3857A, A25056G, C27389T, A29567G
CovSpectrum Query: Nextcladepangolineage:CH.1.1* & [3-of: C22458T, G22770A, A25056G, C27389T, A29567G]
Substitutions on top of XBB.1.5:
Spike: T299I, R403K, D1165G
ORF1a: A698T
ORF10: I4V
Nucleotide: G2357A, C22458T, G22770A, A25056G, C27389T, A29567G

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/CH.1.1_T299I%2CR403K%2CD1165G_subtreeAuspice1_genome_ac74_719fe0.json

Evidence
This lineage only showed up very recently but appears to be growing quickly in England. It's possible it's a local outbreak that will die out quickly, as we've seen in England before, but the sequences come from three different originating labs, which I believe indicates they came from different locations in England.

The ACE2 affinity of CH.1.1 is weak, probably the weakest of any widely circulating variant—lower than XBB* lineages that still have S:F486S, for example. It seems possible an increase in ACE2 affinity could improve CH.1.1's fitness similar to how S:S486P increased XBB* fitness (though the magnitude of CH.1.1's increase would almost certainly be much smaller). See measured ACE2-binding affinity below as measured by Yunlong Cao, et al. in "Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution." https://www.nature.com/articles/s41586-022-05644-7

S:R403K is, according to the Bloom Lab RBD heat map one of the few known spike mutations to substantially enhance ACE2 affinity on a BA.2 background. https://jbloomlab.github.io/SARS-CoV-2-RBD_DMS_Omicron/RBD-heatmaps/

S:T299I has been seen at low levels throughout the pandemic, and its fitness effects seem neutral. The nucleotide for this mutation is surrounded on both sides by two adenines, which is a perfect context for APOBEC-caused deamination, leading to C->T substitution, so this is the likely cause of T299I.

S:D1165G is much less common, only appearing in 18 sequences outside this lineage in the past three months.

Genomes (Note: 8/16 sequences are visible on the Usher tree but are not yet on GISAID and so are not included below)

Genomes

EPI_ISL_16937741, EPI_ISL_17016814, EPI_ISL_17032431, EPI_ISL_17097378, EPI_ISL_17098175, EPI_ISL_17098700, EPI_ISL_17105228, EPI_ISL_17105510

[oobb45729]

T299I actually is not far from Q613H, and they were seen together in some AY.33s.
T299I is even closer to Q314 and T315, which could interact with K764.

[thomasppeacock]

This looks very interesting - going to stick a monitor label on it but if it grows for another week or so I think we should designate it.

[FedeGueli]

I count 26 sequences of this one now on Usher:

[Memorablea]

Thank you! It has been specified as CH.1.20!e3c981f

[FedeGueli]

Thank you! It has been specified as CH.1.20!e3c981f

CH.1.1.20