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Title: Impact of Missense Mutations on Spike Protein Stability and Binding Affinity in the Omicron Variant
The global effort to combat the COVID-19 pandemic faces ongoing uncertainty with the emergence of Variants of Concern featuring numerous mutations on the Spike (S) protein. In particular, the Omicron Variant is distinguished by 32 mutations, including 10 within its receptor-binding domain (RBD). These mutations significantly impact viral infectivity and the efficacy of vaccines and antibodies currently in use for therapeutic purposes. In our study, we employed structure-based computational saturation mutagenesis approaches to predict the effects of Omicron missense mutations on RBD stability and binding affinity, comparing them to the original Wuhan-Hu-1 strain. Our results predict that mutations such as G431W and P507W induce the most substantial destabilizations in the Wuhan-Hu-1-S/Omicron-S RBD. Notably, we postulate that mutations in the Omicron-S exhibit a higher percentage of enhancing binding affinity compared to Wuhan-S. We found that the mutations at residue positions G447, Y449, F456, F486, and S496 led to significant changes in binding affinity. In summary, our findings may shed light on the widespread prevalence of Omicron mutations in human populations. The Omicron mutations that potentially enhance their affinity for human receptors may facilitate increased viral binding and internalization in infected cells, thereby enhancing infectivity. This informs the development of new neutralizing antibodies capable of targeting Omicron’s immune-evading mutations, potentially aiding in the ongoing battle against the COVID-19 pandemic.  more » « less
Award ID(s):
2000296
PAR ID:
10595219
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
MDPI
Date Published:
Journal Name:
Viruses
Volume:
16
Issue:
7
ISSN:
1999-4915
Page Range / eLocation ID:
1150
Subject(s) / Keyword(s):
SARS-CoV-2 COVID-19 Spike protein Omicron Variant computational saturation mutagenesis
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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