Acquisition of the L452R Mutation in the ACE2-Binding Interface of Spike Protein Triggers Recent Massive Expansion of SARS-CoV-2 Variants

Figures

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  FIG 1. Distribution of silent (green triangles) and amino acid (red triangles) mutations across region 414 to 583 of the spike protein. Dark red, receptor-binding domain (RBD); green, C-terminal domain 1 (CTD1) of S1 spike region; blue, receptor-binding ridge epitope residues; yellow, 443-to-450 loop epitope residues; black, 570-to-572 loop residues.

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  FIG 2. Phylogenetic trees of CAL.20A and the epsilon variant genomes. (A) nCoV strains identified in the tested samples. (B) nCoV strains deposited into GISAID database.

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  FIG 3. Nextstrain-generated radial cladogram of SARS-CoV-2 genetic variants (as of 12 June 2021). Showing 519 of 3,883 genomes randomly sampled between Jun 2020 and May 2021, belonging to 23 PANGO lineages. Circles tip branches containing genomes with any mutation in L452 (circles on branches without the mutations were manually removed for a visual clarity). Yellow circles, branches with L452R; blue, with L452Q; orange, with L452M. Black triangle tips the branch of lineage that includes CAL.20A. (At the date of analysis, CAL.20A strains were not among the sampled genomes in the Nextstrain database, and only three B.1.232 [all non-CAL.20A] lineages were found). Nomenclature: PANGO lineage followed by Nextstrain clade in parenthesis and the current VOC/VOI designation. In red, VOC/VOI with an omnipresent or nearly omnipresent L452 mutation (VOC beta is in black, as the L452 mutation is found only in few genomes of the variant).