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      Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

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          Abstract

          Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants including BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants as well as their ancestral BA.4/5, BA.2.75 and D614G variants against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its key F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the key N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.

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          Author and article information

          Contributors
          Journal
          bioRxiv
          October 20 2022
          Article
          10.1101/2022.10.19.512891
          36476380
          c244729b-e7f6-47eb-aaa7-4463961b8f5c
          © 2022
          History

          Microbiology & Virology
          Microbiology & Virology

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