Recent studies, including ours, have suggested that L452R 4, 5, 6, 7, 8, 9, N460K 2, 6, 10, 11, and R346T 2 increase the binding affinity of the SARS-CoV-2 S protein to human angiotensin-converting enzyme 2 (ACE2), the receptor for viral infection, while R346T 12, 13, K444T 13 and F486V 2, 4, 5, 13, 14, 15 contribute to evasion of antiviral humoral immunity induced by vaccination and natural SARS-CoV-2 infection. For instance, the Omicron BQ.1.1 variant, which is a descendant of Omicron BA.5 and is becoming predominant in Western countries 1 as of December 2022, possesses all convergent substitutions, such as R346T, K444T, L452R, N460K, and F486V. As of December 2022, recently emerging Omicron subvariants are undergoing convergent evolution, acquiring substitutions at the same residues of the spike (S) protein, such as R346, K444, L452, N460, and F486 2, 3. The SARS-CoV-2 Omicron variant has been the current variant of concern since the end of 2021 1. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity.
XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022.
In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Nature Communications volume 14, Article number: 2800 ( 2023) The Genotype to Phenotype Japan (G2P-Japan) Consortium,.Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants
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