Kannan, S.R.; Spratt, A.N.; Sharma, K.; Goyal, R.; Sönnerborg, A.; Apparsundaram, S.; Lorson, C.L.; Byrareddy, S.N.; Singh, K. Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions. Int. J. Mol. Sci.2022, 23, 5534.
Kannan, S.R.; Spratt, A.N.; Sharma, K.; Goyal, R.; Sönnerborg, A.; Apparsundaram, S.; Lorson, C.L.; Byrareddy, S.N.; Singh, K. Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions. Int. J. Mol. Sci. 2022, 23, 5534.
BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.
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