Structural Insight into Antibody Evasion of SARS-Cov-2 Omicron Variant

Abstract

The SARS-CoV-2 continues to mutate and evolve with the emergence of omicron as the new variant of concern. The omicron variant has a large set of mutations occurring in the gene encoding spike protein. About half of these mutations are specifically located in the receptor binding domain (RBD), reflecting their significance in ACE2 interaction and antibody recognition. We have carried out the present study to understand how these mutations structurally impact the binding of the antibodies to their target epitope. We have computationally evaluated the binding of different RBD targeted antibodies, namely, CB6 (etesevimab), REGN10933 (casirivimab), S309 (sotrovimab), and S2X259 to the omicron mutation-induced RBD. All the four antibodies show reduced binding affinity towards the omicron RBD. The therapeutic antibody CB6 aka etesevimab was substantially affected due to numerous omicron mutations occurring in its target epitope. This study provides a structural insight into the reduced efficacy of RBD targeting antibodies against the SARS-CoV-2 omicron variant.