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cov-lineages / pango-designation

Repository for suggesting new lineages that should be added to the current scheme
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BA.2.3 Sublineage with 10 highly convergent S1 mutations (5 seqs, 3xSingapore, 1xAustralia, 1xUSA) #1013

Closed ryhisner closed 2 years ago

ryhisner commented 2 years ago

Description Sub-lineage of: BA.2.3 Earliest sequence: 2022-8-15, USA, California — EPI_ISL_14744358 Most recent sequence: 2022-8-24, Singapore — EPI_ISL_14727166 Countries circulating: Singapore (2 local cases), Australia (1), USA (1) Number of Sequences: 4 Substitutions on top of BA.2.3: Spike: M153T, N164K, H245N, G257D, K444R, N450D, L452M, N460K, E484R, R493Q (R) ORF1a: T727I, A1049V, I1714T, M2169V, T2174I, T2648I, Q3922R ORF1b: T1404M Nucleotide: C1471T, C2445T, T5406C, A6770G, C6786T, C8208T, C10189T, A12030G, C17678T, C18252T, T22020C, T22054G, C22295A, G22332A, A22893G, A22910G, C22916A, T22942G, G23012A, C23013G, C28550A

USHER Tree https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/subtreeAuspice1_genome_7869_f60fb0%E2%80%94BA.2.3%E2%80%94Beast.json Screen Shot 2022-08-31 at 5 27 56 PM

Evidence This is an extraordinary saltation, and four sequences have suddenly showed up in three countries very distant from one another. It contains numerous convergent mutations in spike, as well as a very rare 2-nucleotide mutation with S:A484R. As @Sinickle has pointed out to me, the path to A484 to R484 requires an intermediate stop at either G484 or T484, both very uncommon. Both cases in Singapore are described as local cases, suggesting it has been circulating there to some extent. This is also suggested by the additional mutations found in one Singapore sequence (S:N17S, ORF1a:A1049V, and nuc A126G). The earliest sequence is from the United States, quite far removed from the other three, suggesting this might already be geographically widespread.

Genomes EPI_ISL_14723265 EPI_ISL_14727166 EPI_ISL_14736013 EPI_ISL_14744358

ryhisner commented 2 years ago

One of the two sequences uploaded so far today from Australia has the rare S:P499H mutation. EPI_ISL_15301179

S:P499 is an RBD antibody-escape site. According to the Bloom Lab RBD Escape Calculator, for BA.5 convalescents (who had been previously infected or vaccinated), it's the 9th most prominent RBD escape site for antibodies known to neutralize BA.5, behind only R346, F347, K444, V445, G446, G447, N448, and N450. For antibodies known to neutralize BA.2, it falls a few spots lower, but many of the residues ahead of it are already mutated in BA.2.3.20. https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/

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FedeGueli commented 1 year ago

I was analyzing a bit the chinese BA.2.3.20 and only now i realized that Nuc C28550A (defining in BA.2.3.20) corresponds to Orf9b:D89E, probably it was already known by everyone but i put here to save some time to anyone are looking at this variant.

cc @ryhisner @corneliusroemer @thomasppeacock @silcn @InfrPopGen @AngieHinrichs