EG.5.1.1 Saltation: S:K356T, H681R, ORF3a:A72S, N:P365L, ORF1a:P309L, H1141Y, E2112D, V3751F (13 seq, Germany, Austria, USA, France , Italy)

[ryhisner]

Spotted and proposed first by @corneliusroemer in cov-lineages/pango-designation#2327 (comment) (EDITED)

Description

Sub-lineage of: EG.5.1.1
Earliest sequence: 2023-9-28, USA (New Jersey) – EPI_ISL_18379617
Most recent sequence: 2023-10-6, Germany – EPI_ISL_18403336
Countries circulating: Austria (2—one a traveler to USA), Germany (1), USA (1)
Number of Sequences: 4
GISAID Nucleotide Query: T499A, T2633C, C4093A
CovSpectrum Query: Nextcladepangolineage:EG.5* & [-of:]
Substitutions on top of EG.5.1.1.:
Spike: K356T, H681R
N: P365L
ORF3a: A72S
ORF1a: P309L, H1141Y, E2112D, V3751F
Nucleotide: T499A, C1191T, T2633C, C3686T, C4093A, A6601C, G11516T, C13019T, A22629C, A23604G, G25606T, C26534T, A27107C, C27600T, C29367T

Phylogenetic Order of Mutations: All simultaneous (on one branch)

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/EG.5.1.1_Saltation_K356T_H681R_etc.json?c=gt-nuc_499&gmax=1499&label=id:node_3451968
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/EG.5.1.1_Saltation_K356T_H681R_etc.json

Evidence
This is a 15-nucleotide, 8-AA saltation that likely arose in the Austria/Germany region, where very little sequencing is done these days. So this may be more widespread than it appears due to Austria/Germany being an undersequenced region.

One of the four sequences is a Ginkgo Bozoworks sequence from a traveler from Austria. On the Usher tree, it appears as if it lacks two mutations the others have, but this is only due to the usual awful coverage from Ginkgo, one of the worst labs around, yet which somehow received the federal contract to do some of the most important sequencing of all (airport travel sequences in the US).

This lineage also has the 3-nuc ORF9b/N TRS extended homology at the end of ORF8, and I think it's likely this was part of the saltation as well. This is a homoplasic mutation though, so Usher groups it with a few other small branches.

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Genomes

Genomes

EPI_ISL_18379617, EPI_ISL_18385103, EPI_ISL_18400043, EPI_ISL_18403336

[FedeGueli]

Thx Ryan great catch! i have 5 sequences with the earliest being :

hCoV-19/USA/NY-CDC-QDX85770892/2023 | Original | EPI_ISL_18379617 | 2023-09-28 | 2023-10-12

[oobb45729]

Any idea about what ORF1a:P309L/Q does?

[ryhisner]

Any idea about what ORF1a:P309L/Q does?

Nope. I only have a vague idea of what NSP2 does—probably RNA binding and some sort of interaction with cell translational machinery, I guess? I usually get interested and start researching a protein when I see a mutation in it that appears over and over in chronic-infection sequences, and there just aren't any such mutations in NSP2.

[FedeGueli]

8 now, it doesnt seem fast but better to track it futher

[FedeGueli]

+1 Germany

[FedeGueli]

+2 NY +2 Germany

[FedeGueli]

I didnt notice that was spotted and proposed by @corneliusroemer first in cov-lineages/pango-designation#2327 (comment) , as he now closed his issue i will keep this one open for a while more.

[ryhisner]

Ha, I even commented on that one and apparently had completely forgotten about it three days later.

[corneliusroemer]

Same here, there are now 4 more sequences. I'll designate so we don't rediscover it eternally :D

hCoV-19/Germany/BY-MVP-000022359/2023|EPI_ISL_18540634|2023-11-09
hCoV-19/France/GES-IPP26961/2023|EPI_ISL_18540929|2023-11-06
hCoV-19/Switzerland/BS-UHB-USB_20_dc2d011e/2023|EPI_ISL_18543363|2023-11-07
hCoV-19/Switzerland/BL-UHB-USB_20_c7e91af2/2023|EPI_ISL_18543400|2023-11-04

[FedeGueli]

Designated HK.25 via cov-lineages/pango-designation@0c6878b