JN.1 with S:K444R, S:Y453F (14 seq, 13 Brazil, 1 USA; Feb 15)

[ryhisner]

Description

Sub-lineage of: JN.1 (BA.2.86.1.1)
Earliest sequence: 2024-1-1, Brazil, Bahia, Anguera — EPI_ISL_18864440
Most recent sequence: 2024-1-13, Brazil, Bahia, Salvador — EPI_ISL_18864483
Continents circulating: South America (13)
Countries circulating: Brazil (13)
Number of Sequences: 13
GISAID Nucleotide Query: A22920T, A22893G, C897A
CovSpectrum Query: Nextcladepangolineage:JN.1* & [2-of: C6696T, A22920T]
Substitutions on top of JN.1:
Spike: K444R, Y453F
ORF1a: A307V, P2144L
Nucleotide: C1185T, C6696T, A22893G, A22920T, A24457G

Phylogenetic Order of Mutations: C1185T (ORF1a:A307V) → A22893G, A24457G (S:K444R) → C6696T, A22920T (ORF1a:P2144L, S:Y453F)

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/JN.1_K444R_Y453F.json?c=gt-S_453&gmax=25384&gmin=21563&label=id:node_6898349

Evidence
S:Y453F is a mutation known to cause a large increase in ACE2 binding. This could create space for JN.1 to add more RBD mutations. 12/13 sequences appear to lack S371F, but this is almost certainly an artifact since multiple unrelated sequences from the same upload also appear to lack S371F. The N417K "reversion" is present in a huge proportion of sequences from Brazil, so that can be dismissed as well. There is a lot of dropout in these sequences, so any reversion should be presumed artifactual until proven otherwise.

All of these have collection dates in 2024, the first on January 1, the most recent January 13. One sequence is from Rio de Janeiro and the rest are from the Brazilian state Bahia, but they come from 11 different cities in Bahia: Amelia Rodrigues, Anguera, Camacari, Camamu, Conceicao da Feira, Feira de Santana, Ipira, Madre de Deus, Mirangaba, Nova Itarana, and Salvador.

Genomes

Genomes

EPI_ISL_18834387, EPI_ISL_18864439-18864440, EPI_ISL_18864445-18864446, EPI_ISL_18864449, EPI_ISL_18864453, EPI_ISL_18864462, EPI_ISL_18864469, EPI_ISL_18864472-18864474, EPI_ISL_18864483,

[Sinickle]

XBB.1 was a variant that clearly benefited from having more ACE2 affinity than it started with. There are two versions of it circulating today, both of which have increased ACE2 affinity: ones with S:F486P, and ones with S:R403K.
There was a third kind that died out some time ago, but still outlived the XBBs that had neither S:F486P nor S:R403K: the XBBs with S:Y453F.

Since JN.1 already has S:F486P and S:R403K, S:Y453F makes a lot of sense as a mutation that could become important if it is still able to make use of having more binding affinity.

[HynnSpylor]

Oh sorry I duplicate in sars-cov2-lineage proposal.
S:Y453F is generally considered to improve hACE2 binding largely, however, its actual impact is still controversial.

[FedeGueli]

Interestingly EPI_ISL_18864442
(hCoV-19/Brazil/BA-LACEN-293405735/2024) shown in the tree has Orf1a:P2144L without S:Y453F, collected in Bahia Camacari
https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice1_genome_test_12a62_220dd0.json?label=id:node_6898483
Not apparent dropout. It could be basal to this lineage or hinting to base calling

[RajLABN]

JN.1.5* from NZ with S:Y453F (EPI_ISL_18850281) -good overlap but without K444R

[corneliusroemer]

Very interesting one - unfortunately quite a bit of reversions there so might be good to get a non-Brazilian sample for confirmation.

Usher with reversions highlighted:

There are two non-Brazil sequences with 444R but none yet with 453F (England and USA/GBW).

[FedeGueli]

@corneliusroemer @ryhisner
there maybe a couple of sequences of this with dropout in 444-453 region which are misplaced by Usher in other places

EPI_ISL_18872374

EPI_ISL_18872372

Both from Espirito Santo state but two cities

Tree:

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/subtreeAuspice2_genome_test_300a7_a0ad50.json?label=id:node_6879877
the fact they are bboth in a W452L branch makes me think that also the one with coverage at 453 in reality is just base calling.

Best view is downsampled tree:

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/singleSubtreeAuspice_genome_test_300a7_a0ad50.json?f_userOrOld=uploaded%20sample&label=id:node_6876283

They both have further acquired beneficiail S:V1264L

[FedeGueli]

Moreover : a potential query : C1185T, C6696T,T3565C finds 16 : the original 13 + 2 >Espirito Santo plus one not found but put in the 453F tree by Usher:

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/singleSubtreeAuspice_genome_test_4387d_a10600.json?f_userOrOld=uploaded%20sample&label=id:node_6906739

[HynnSpylor]

First seq outside Brazil is detected (in FL, US-EPI_ISL_18895609)

[FedeGueli]

@HynnSpylor

and very recent , February.

[ryhisner]

First seq outside Brazil is detected (in FL, US-EPI_ISL_18895609)

Branches off the only Brazilian sequence with OF9b:T83I, a somewhat homoplasic mutation. Adds ORF3a:P258S as well. Mutations from about ORF3a:240 to the end of ORF3a happen frequently, but I think they're probably inconsequential. Frameshifts + stop codons have happen there with some frequency.

[FedeGueli]

One more Federal District Brazil collected on 24/01 now 18 with C1185T, C6696T,T3565C

[FedeGueli]

thank you @corneliusroemer

[ryhisner]

One just showed up in Queensland, Australia. Collection date February 3. EPI_ISL_18915659

[FedeGueli]

One just showed up in Queensland, Australia. Collection date February 3. EPI_ISL_18915659

this is fast to me

[RajLABN]

Two more from USA (CA 2/11 & 2/13 collection dates) - EPI_ISL_18917950, EPI_ISL_18918041

[FedeGueli]

Here the new tree:

https://nextstrain.org/fetch/genome-test.gi.ucsc.edu/trash/ct/singleSubtreeAuspice_genome_test_5f5f5_6fb530.json?f_userOrOld=uploaded%20sample&label=id:node_6882804

Assessing further mutations i would note that:
The Canadian sample and the two coming from Espirito Santo 8misplaced in Usher due dropouts) have also S:V1264L ,
the Canadian one also has S:I692F ,S:I692L was defining of the shadowy lineage then designated BA.2.38.4 that emerged in India and rapidly spread in 4 continents ( we nicknamed it this way 4 Continents) likely due the fact it emerged in West Bengala. it was then destroyed by the rise of XBB right in that are between Bangladesh and West Bengala.
The sample from Florida clusters with the only one from Rio: it has ORF9b:T83I that was quite good in a late BA.5.1 sublineage circulating at the end of 2022 in Japan ( that surprisingly after getting S:R346T and S:T747I,and getting designated BA.5.1.38 since , managed to survive till August 2023: this means it was resilient versus many global lineages as BA.5.2,BN.1.3, BF.5/BF.7, BQ.1/BQ.1.1/ XBB.1.5,XBB.1.9/XBB.1.16/ EG.5.1 and giving up just versus FLip lineages) while the Californian samples have S:K529N that pops up frequently without big signs of any advantage as of today.
There are mutations in NSP3 and other NSPs sparse along the tree, maybe @ryhisner has looked or will look at them.