BA.5.2.46 Molnupiravir Lineage Circulating(?) in Western Australia + Related Recombinant (7 seq, June 6)

[ryhisner]

Description

Sub-lineage of: BA.5.2.46 Earliest sequence: 2023-3-3 — EPI_ISL_17187405 Most recent sequence: 2023-5-11 — EPI_ISL_17765632 Countries circulating: Australia (7) Number of Sequences: 7 GISAID AA Query: Spike_A264T, NSP2_A80V, NSP3_A1321V, NSP3 V1420I GISAID Nucleotide Query: G3974A, G6977A, G14250A, G17972A, G19254A CovSpectrum Query: Nextcladepangolineage:BA.5.2.46* & [9-of: C1044T, T1066C, G2117A, C2388T, T3578C, G3974A, C5183T, G6977A, G13118A, G14250A, G17972A, G19106A, G19254A, G21606T, G21608T, G22352A, C23741T, C25549T, T27402C] Substitutions on top of BA.5.2.46: Spike: C15F, V16F, A264T ORF3a: L53F ORF1a: A260V, G618S, T708I, E1237K, V2238I, A4285T (NSP2_A80V, NSP2G438S, NSP2 T528I, NSP3_E419K, NSP3_V1420I, NSP10_A32T) ORF1b: R1502K, C1880Y (NSP13_R579K, NSP14_C356Y) Nucleotide: C1044T, T1066C, G2117A, C2388T, T3578C, G3974A, C5183T, G6977A, G13118A, G14250A, G17972A, G19106A, G19254A, G21606T, G21608T, G22352A, C23741T, C25549T, T27402C AA Deletions: S:∆Y144, ORF1a:∆82-86, ORF1a:∆141-143 Nucleotide Deletions: ∆509-523, ∆686-694, ∆21992-21994, ∆27572-27597

USHER Tree https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/MOV_BA.5.2.46_AUS,WA_2023_5_11__7seq.json?c=gt-S_15&label=id:node_8863779

Evidence The molnupiravir signature in this one is clear, as pictured below. The 9/19 G→A nucleotide mutations are a dead giveaway. The only transversions are a very strange duo of G→T mutations, G21606T & G21608T, which result in S:C15F and S:V16F, an extremely rare mutational combination. S:C15F is known to alter the signal peptide cleavage location, eliminate a disulfide bond (between S:C15 and S:C136 if I remember right), and radically restructure the NTD.

All sequences here have a 26-nucleotide ORF7a deletion (∆27572-27597) that causes a frameshift.

The long molnupiravir branch is disrupted because an apparent complex recombinant between a sequence from this lineage and an XBB of some sort. ORF1ab (and probably spike through S:213) and the region from 25416-27384 seem to have been taken from the XBB with most of the remainder from this BA.5.2.46 lineage. It's possible this sequence is an artifact due to contamination. The odd inclusion of one private mutation from this BA.5.2.46 branch within the XBB* portion of ORF1b seems suspicious.

MOV-Lineage Genomes

Genomes

EPI_ISL_17187405, EPI_ISL_17374733, EPI_ISL_17374799, EPI_ISL_17374806, EPI_ISL_17527471, EPI_ISL_17527567, EPI_ISL_17765632

Recombinant Genome

Genomes

EPI_ISL_17661357

[FedeGueli]

Note that the entire branch evolved from a route defined by NSP6_C221F ( curiously again G > T , G11634T) I dont know anything on NSP6 but @zach-hensel maybe could help what could mean a lose of a cysteine there, i suspect it could be relevant.

[FedeGueli]

No new sequence of this closing for now.