FL.2 with S:N641K emerged likely in Eastern Africa and shows a lot of Spike diversity: three branches 259S / 809T / 471Q (79 seqs, 14 countries)

[NkRMnZr]

Transferred from sars-cov-2-variants/lineage-proposals#520

Defining Mutations: FL.2 > C25521T > T23485A(S:N641K), A29683T
Query: T23485A, C25521T
Earliest seq: 2023-03-15 (EPI_ISL_17363241, England, UK)
Latest seq: 2023-08-03 (EPI_ISL_18089995, Sweden)
Sampled Countries: USA (23; California/16, Arizona/4, New York/2, Texas/1), Sweden (21), 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, EPI_ISL_18057063, EPI_ISL_18069764, EPI_ISL_18069768, EPI_ISL_18069925, EPI_ISL_18089985, EPI_ISL_18089987, EPI_ISL_18089990, EPI_ISL_18089995

UShER:
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_432ef_8c6650.json?f_userOrOld=uploaded%20sample

Trivia:

• S:N641K only sampled 170 times during the whole pandemic, about 1/3 is from this branch. It may be associated with novel cleavage site of HAT (see comment by @thiolist ), related study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167920/
• 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, all forms some kind of long 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:E484S), C24210T(S:T883I)
3. G1820A(ORF1a:G519S) > G22973C(S:E471Q), C27389T(TRS of ORF7a), A28319G(N:T16A), C29696T

[ryhisner]

Continuing the discussion from the previous page, it seems like a HAT cleavage site at S:R667 may have played an important role in SARS-CoV-1, at least according to this paper. https://journals.physiology.org/doi/full/10.1152/ajplung.00509.2016

[ryhisner]

It appears that a HAT cleavage site promotes cell-cell fusion, something we haven't seen a great deal of since Delta. https://journals.asm.org/doi/10.1128/jvi.05300-11

.

[FedeGueli]

It appears that a HAT cleavage site promotes cell-cell fusion, something we haven't seen a great deal of since Delta. https://journals.asm.org/doi/10.1128/jvi.05300-11

.

Now i am extending a bit too much ( also Sars1 not having the FCS could have an impact) but S:I666V in BQ.1.2 was the only mutation found experimentally in cell lines to bring back fusogenictity to pre omicron era. Wondering if linked. c @thomaspeacock

[FedeGueli]

The emergence in Eastern Africa is deduced by two early (march-april) samples from airport surveillance from Kenya and Somalia cc @corneliusroemer see original issue for more info.

[thiolist]

Hello Fredrico, I use the software tool "Peptide Cutter". https://web.expasy.org/peptide_cutter/ When given the test sequence ...GS*N*VF.... (and the "Trypsin" optimized analysis is enabled) this is the result: [image: Peptide cutter result for "GSNVF" sequence.png] *No cleavage *(from Trypsin or any other enzyme supported by Peptide Cutter). But the sequence ...S*K*V... produces: [image: Peptide cutter result for "GSKVF" sequence.png] *100% cleavage* (if the enzyme has access to the ...GS*K*VF... sequence). Interestingly, TMPRSS2 (another trypsin-like protease) is membrane bound. The spile only becomes available to this enzyme after it has become bound to ACE2 at the cellular membrane. Conversely, the HAT enzyme is soluble, so the spike is continuously available to this enzyme prior to binding to ACE2. Therefore, the spike that antibodies "see" prior to ACE2 binding can have this site already cleaved, and therefore not be recognized by the antibody. *IMPORTANT* Tissues other than the human airway will not have this site cleaved by HAT, and therefore antibodies that target this site on the spike should still function in the rest of the body. - thiolist (Michael Ott)

…

On Sun, Aug 13, 2023 at 5:35 AM Federico Gueli ***@***.***> wrote: The emergence in Eastern Africa is deduced by two early (march-april) samples from airport surveillance from Kenya and Somalia — Reply to this email directly, view it on GitHub <#2180 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/BB4KZSWGGVIA77DGUWACEHLXVDC2NANCNFSM6AAAAAA3OTKPK4> . You are receiving this because you were mentioned.Message ID: ***@***.***>

[thiolist]

[FedeGueli]

Thank you @th

[NkRMnZr]

Tracking updates:

08-18, 2 seqs from USA

EPI_ISL_18099186, EPI_ISL_18104509

08-22, 4 seqs from USA

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_11928_4bf8d0.json?f_userOrOld=uploaded%20sample&label=id:node_6965878

EPI_ISL_18115331, EPI_ISL_18121100, EPI_ISL_18121117, EPI_ISL_18121926

08-30, 3 seqs from USA

EPI_ISL_18143941, EPI_ISL_18145562, EPI_ISL_18160140

[FedeGueli]

both w 259S