Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

• Klíčová slova
• BA.1, BA.2, COVID-19, Omicron, SARS-CoV-2, fusogenicity, growth capacity, immune resistance, pathogenicity,
• MeSH
• COVID-19 virologie   MeSH
• genom virový * genetika   MeSH
• glykoprotein S, koronavirus * genetika   MeSH
• lidé MeSH
• mutace * MeSH
• SARS-CoV-2 * genetika   patogenita   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glykoprotein S, koronavirus * MeSH
• spike protein, SARS-CoV-2 MeSH Prohlížeč

• MeSH
• COVID-19 * MeSH
• lidé MeSH
• SARS-CoV-2 * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

• MeSH
• biotest MeSH
• COVID-19 * MeSH
• fylogeneze MeSH
• křečci praví MeSH
• neutralizující protilátky MeSH
• protilátky virové MeSH
• SARS-CoV-2 genetika   MeSH
• substituce aminokyselin MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• neutralizující protilátky MeSH
• protilátky virové MeSH

• MeSH
• COVID-19 * MeSH
• lidé MeSH
• SARS-CoV-2 * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH