FL.2 with S:N641K (70 seqs, 14 countries) emerged likely in Eastern Africa and shows a lot of Spike diversity: three branches 259S/ 809T/ 471Q

[NkRMnZr]

Defining Mutations: FL.2 > C25521T > T23485A(S:N641K), A29683T Query: T23485A, C25521T Earliest seq: 2023-03-15 (EPI_ISL_17363241, England, UK) Latest seq: 2023-07-13 (EPI_ISL_18055042, California, USA) Sampled Countries: USA (19, California/13, Arizona/4, New York/2), Sweden (17), Canada (9, Ontario), UK (6, England/5, Scotland/1), France (2), Austria (1), China (1, Shanghai), Germany (1), India (1), Ireland (1), Israel (1), Italy (1), Japan (1), Spain (1)

Genomes:

`EPI_ISL_17363241, EPI_ISL_17395881, EPI_ISL_17400810, EPI_ISL_17448553, EPI_ISL_17488308, EPI_ISL_17488334, EPI_ISL_17511907, EPI_ISL_17514054, EPI_ISL_17537803, EPI_ISL_17537913, EPI_ISL_17549297, EPI_ISL_17553672, EPI_ISL_17555869, EPI_ISL_17558172, EPI_ISL_17590487, EPI_ISL_17630281, EPI_ISL_17630455, EPI_ISL_17630478, EPI_ISL_17664440, EPI_ISL_17668930, EPI_ISL_17668978, EPI_ISL_17668999, EPI_ISL_17690272, EPI_ISL_17713615, EPI_ISL_17721736, EPI_ISL_17722643-17722644, EPI_ISL_17722718, EPI_ISL_17731144, EPI_ISL_17731521, EPI_ISL_17732731, EPI_ISL_17732763, EPI_ISL_17732771, EPI_ISL_17732773, EPI_ISL_17732812, EPI_ISL_17732815, EPI_ISL_17732819, EPI_ISL_17764343, EPI_ISL_17764728, EPI_ISL_17767911, EPI_ISL_17768311, EPI_ISL_17769714, EPI_ISL_17781527, EPI_ISL_17791659, EPI_ISL_17797041, EPI_ISL_17809292, EPI_ISL_17809729, EPI_ISL_17838302, EPI_ISL_17838841, EPI_ISL_17854148, EPI_ISL_17855011, EPI_ISL_17950471, EPI_ISL_17950512, EPI_ISL_17951643, EPI_ISL_17981065, EPI_ISL_18005336, EPI_ISL_18010050, EPI_ISL_18045881, EPI_ISL_18046161, EPI_ISL_18046249, EPI_ISL_18046277, EPI_ISL_18055042`

UShER: https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_36e64_922b50.json?f_userOrOld=uploaded%20sample

Trivia:

• No idea what S:N641K does, but it does seems to have a lot of positive charge. Only sampled 170 times during the whole pandemic, about 1/3 is from this branch.
• Not a fast lineage, but got sampled here and there sparsely.
• One of the most recent branch is the one with the most spike mutations, follows: S:259S, E554A and K356N, but there are also mutations like S:P809T, E471Q from other branches.

[NkRMnZr]

Tracking updates:

08-05, 4 seqs from USA: EPI_ISL_18057063, EPI_ISL_18069764, EPI_ISL_18069768, EPI_ISL_18069925 08-11, 4 seqs from Sweden, mini-saltation with S:A484S and S:T883I

[NkRMnZr]

08-11, 4 seqs from Sweden, mini-saltation with S:A484S and S:T883I : EPI_ISL_18089985, EPI_ISL_18089987, EPI_ISL_18089990, EPI_ISL_18089995

UShER for seqs submitted since Aug 1:

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_4208_737740.json?f_userOrOld=uploaded%20sample

Now it already forms 3 different mini-saltation branches:

1. A29683T > C29098T > G4357A > A22337T(S:T259S) > C2942T, C11396T(ORF1a:L3711F), A23223C(S:E554A), C29108T(N:P279S)
2. A29683T > C23987A(S:P809T) > C8016T(ORF1a:A2584V), T15276C, G17032A(ORF1b:V1189I), A21137G(ORF1b:K2557R), G23012T(S:A484S), C24210T(S:T883I)
3. G1820A(ORF1a:G519S) > G22973C(S:E471Q), C27389T(TRS of ORF7a), A28319G(N:T16A), C29696T

[FedeGueli]

Although this has no growth advantage: https://cov-spectrum.org/explore/World/AllSamples/Past3M/variants?aaMutations=Orf1b%3AD54N&nucMutations1=T23485A%2CC25521T&analysisMode=CompareToBaseline&

I think the remarkable spike diversity shown in its tree strongly points to an undersampled circualtion somewhere. EPI_ISL_17395881 collected in Japan back in March from a traveller coming from Somalia and EPI_ISL_17537913 collected earlier in April from a traveller from Kenya could throw some lights on which is that undersampled area.

So i think it should be proposed in the main page specifying these two seqeucnes and the spike diversity shown: (three big branches each with S:259S or S:P809T or S:E471Q as highlighted above by @NkRMnZr )

Ping @corneliusroemer lineage from an undersampled area with a lot of S diversity.

[thiolist]

NkRMnZr asked what S:N6411K does. One thing is that it adds a proteolytic cleavage site that is a target of the HAT (Human Airway Trypsin-like) protease, which could cleave the spike protein at this site. This would change the protein shape in the airway (nasal passage to lungs) without changing its shape elsewhere in the body (e.g. change transmissibility without affecting infectability of tissues outside of the airway).

[FedeGueli]

NkRMnZr asked what S:N6411K does. One thing is that it adds a proteolytic cleavage site that is a target of the HAT (Human Airway Trypsin-like) protease, which could cleave the spike protein at this site. This would change the protein shape in the airway (nasal passage to lungs) without changing its shape elsewhere in the body (e.g. change transmissibility without affecting infectability of tissues outside of the airway).

References?

[NkRMnZr]

NkRMnZr asked what S:N6411K does. One thing is that it adds a proteolytic cleavage site that is a target of the HAT (Human Airway Trypsin-like) protease, which could cleave the spike protein at this site. This would change the protein shape in the airway (nasal passage to lungs) without changing its shape elsewhere in the body (e.g. change transmissibility without affecting infectability of tissues outside of the airway).

Thanks! Any ref to the study?

[FedeGueli]

NkRMnZr asked what S:N6411K does. One thing is that it adds a proteolytic cleavage site that is a target of the HAT (Human Airway Trypsin-like) protease, which could cleave the spike protein at this site. This would change the protein shape in the airway (nasal passage to lungs) without changing its shape elsewhere in the body (e.g. change transmissibility without affecting infectability of tissues outside of the airway).

Thanks! Any ref to the study?

@thomaspeacock pointed to this one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167920/

[ryhisner]

Thanks, Fede. However, I don't think that study says anything about S:N641K creating a HAT cleavage site. Instead, it claims—convincingly, I think—that a cleavage site already exists at S:Y636.

This isn't to say that N641K couldn't create a HAT cleavage site (something I'm not familiar with at all), only that I don't see any support for that idea in this paper.

[NkRMnZr]

Transferred to github.com/cov-lineages/pango-designation#2180

[FedeGueli]

Thx @ryhisner for clarifying!

[FedeGueli]

FL.2.6 via https://github.com/cov-lineages/pango-designation/commit/1fbcb3b49973869d85542990ba04b27b046d659a