Saltation XBB.1.5.32 with S:S31F, N148D, R190S, G257S, K440R S490P, A570V and a double PLPro mutation- 3 sequences ( Illinois, NY)

[corneliusroemer]

Came up high in ACE2 binding score, due to 403K

Seems to be XBB.1.5.32 that has picked up some 11 Spike mutations (not sure about the reversions) - also has the 69/70del

Baseline surveillance from 20yo female. Looks like a chronic spillover

Strain: hCoV-19/USA/NY-CDC-QDX84735142/2023 EPI_ISL: EPI_ISL_18276415

Slight convergence with BA.2.86:

• 69/70 deletion
• P1143L
• A570V
• R403K

EDITED ON October 22 (credits to @Sinickle for pointing this):

Mutations shared by all thre sequences : Orf1a:T1638I (PLPro_T75I) Orf1a: I1714V (PLPro_I151V) Spike: S31F, N148D,R190S, G257S, K440R S490P, A570V ORF3a:H182Y M:I82V ORF8 :I74L

Query : C5178T, A5405G, C16848T (NEW) finds 3 : EPI_ISL_18276415, EPI_ISL_18359229, EPI_ISL_18414808,

Tree: https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_3f7c0_4bd990.json?label=id:node_3568596

[ryhisner]

Two interesting reversions here: S:I19T reestablishes the N17 glycan, which was lost with T19I, and S:S446G is a common reversion in BA.1 chronic-infection sequences.

ORF1a:T1638I is the single most common non-spike mutation I see in chronic sequences. It's a change to the kind of hydrophobic residue SARS-CoV-1 has at that site (L), and which has been shown to increase the ability of the papain-like protease (PLpro) to cleave K48-linked ubiquitin chains. ORF1a:K1795Q, the 2nd-most common non-spike mutation in chronic sequences, has the same effect.

P1143S/L seems to be increasingly common in these saltation variants. I know Jesse Bloom's lab has found mutations at this site to be extremely successful in cell culture experiments. P1162S/L is another fairly common one. S2 is pretty much a complete mystery at this point, so I don't think there's much hope of deciphering what effect these mutations have.

[krosa1910]

Ryan is such a genius, that I don't have much to say regarding this variant besides what he already concluded. I do know from Cao's research that K440R is providing medium-level escape, and since it is not a reversion probably it does not lose escape to older infection.

[ryhisner]

Forgot to mention that S:R190S, which was in Gamma, also adds a glycan. So like BA.2.86, this one adds two glycans, though these are both fairly early in the NTD (N17, N188), whereas BA.2.86's glycans are later in the NTD & in the RBD (N245, N354). The N354 glycan seems to come at a pretty steep cost in terms of infectivity though.

[FedeGueli]

Thanks @ryhisner that alignment with Sars cov 1 rocks. Worth mentioning that the PLPro of SC1 was more efficient than SC.2 ( i recall a TWiv EPisode on that with a dedicated paper ). S:R190S is seeing an uptrend (GS.3 for example but also other lineages).

@corneliusroemer do you think this is not the chronic patient but someone infected by a chronic did i get right?

[FedeGueli]

I ve added this specific query: T13339A,C16848T

[corneliusroemer]

Baseline surveillance is what makes me think this is not a chronic but community circulation, but I might be wrong. Speculation doesn't really matter, we will either see more of this or we won't. If we don't it doesn't matter.

[FedeGueli]

Baseline surveillance is what makes me think this is not a chronic but community circulation, but I might be wrong. Speculation doesn't really matter, we will either see more of this or we won't. If we don't it doesn't matter.

Yes for sure thank you. it was for adding or not the single chronic infected patient label or not ;)

[ryhisner]

Baseline surveillance is what makes me think this is not a chronic but community circulation, but I might be wrong. Speculation doesn't really matter, we will either see more of this or we won't. If we don't it doesn't matter.

I'm not sure if labels like baseline surveillance, random surveillance, or sentinel surveillance can ever really be trusted. All Canadian sequences say random surveillance, yet we know a lot of them are targeted at nursing home outbreaks. I see this with sequences from other countries as well. Sometimes repeated sequences that are obviously from the same patient will be labeled as random/baseline/sentinel surveillance.

[FedeGueli]

No new sample of this one closing it for now

[Sinickle]

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_8fd8_2ccf90.json

It's actually alive and spreading. Unique metadata and different counties on the Illinois sequences.

The Illinois sequences have some coverage issues for sure. They both don't cover S:373 and S:484-486 but this seems standard for XBB from this particular lab to not cover those specific areas. I think it looks like both Illinois sequences have S:N148D, and the reversion on S:146 is not legitimate? Also a bit odd that the S:217 reverts on the one sequence.

So then the shared spike mutations are.. I19T, S31F, 69-70del, R190S, D253E, G257S, K440R, S446G, S490P, A570V

New York seq has P217S, R403K, Q675H, P1143L

Illinois seq 1 has N148D, P217S, S408R, N477S

Illinois seq 2 has N148D, L176F, D250N, S408R

[FedeGueli]

Thx @Sinickle

[FedeGueli]

@angiehinrichs these two may be excluded by Usher:EPI_ISL_18359229, EPI_ISL_18414808

[FedeGueli]

I have re arranged the proposal and the headline , it has 7 shared spike mutations. and i have assignes to @ryhisner cause it has also a double PLpro mutation. @Sinickle you are assigned too cause you spotted the fact it was spreading further.

[FedeGueli]

new query : C5178T, A5405G, C16848T

[FedeGueli]

Still just three closing it.