Molecular Insights into Striking Antibody Evasion of SARS-CoV-2 Omicron Variant
Zeng-Shuai Yan1 , Yao Xu1 , Hong-Ming Ding2* , and Yu-Qiang Ma1*
1 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China2 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China
Abstract ：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.
收稿日期: 2022-07-19
出版日期: 2022-09-16
:
87.15.A-
(Theory, modeling, and computer simulation)
87.15.ap
(Molecular dynamics simulation)
87.15.km
(Protein-protein interactions)
87.15.hg
(Dynamics of intermolecular interactions)
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