Molecular Insights into Striking Antibody Evasion of SARS-CoV-2 Omicron Variant

The SARS-CoV-2 Omicron variant has become the dominant variant in the world. Uncovering the structural basis of altered immune response and enhanced transmission of Omicron is particularly important. Here, taking twenty-five antibodies from four groups as examples, we comprehensively reveal the underlying mechanism of how mutations in Omicron induces the weak neutralization by using molecular simulations. Overall, the binding strength of 68% antibodies is weakened in Omicron, much larger than that in Delta (40%). Specifically, the percentage of the weakened antibodies vary largely in different groups. Moreover, the mutation-induced repulsion is mainly responsive for the weak neutralization in AB/CD groups but does not take effect in EF group. Significantly, we demonstrate that the disappearance of hydrophobic interaction and salt bridges due to residue deletions contributes to the decreased binding energy in NTD group. This work provides unprecedented atomistic details for the distinct neutralization of WT/Delta/Omicron, which informs prospective efforts to design antibodies/vaccines against Omicron.