Omicron mutations increase interdomain interactions and reduce epitope exposure in the SARS-CoV-2 spike

TitleOmicron mutations increase interdomain interactions and reduce epitope exposure in the SARS-CoV-2 spike
Publication TypeJournal Article
Year of Publication2023
AuthorsWieczór, Miłosz, Tang Phu K., Orozco Modesto, and Cossio Pilar
JournaliScience
Volume26
Issue2
Pagination105981
Date Published02/2023
ISBN Number2589-0042
KeywordsBioinformatics, Computational molecular modeling, Microbiology, Structural biology
Abstract

SummaryOmicron BA.1 is a highly infectious variant of SARS-CoV-2 that carries more than thirty mutations on the spike protein in comparison to the Wuhan wild type (WT). Some of the Omicron mutations, located on the receptor-binding domain (RBD), are exposed to the surrounding solvent and are known to help evade immunity. However, the impact of buried mutations on the RBD conformations and on the mechanics of the spike opening is less evident. Here, we use all-atom molecular dynamics (MD) simulations with metadynamics to characterize the thermodynamic RBD-opening ensemble, identifying significant differences between WT and Omicron. Specifically, the Omicron mutations S371L, S373P, and S375F make more RBD interdomain contacts during the spike’s opening. Moreover, Omicron takes longer to reach the transition state than WT. It stabilizes up-state conformations with fewer RBD epitopes exposed to the solvent, potentially favoring immune or antibody evasion.

URLhttps://www.sciencedirect.com/science/article/pii/S2589004223000585
Short TitleiScience
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