Journal
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
Volume 13, Issue 17, Pages 3915-3921Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpclett.2c00423
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Funding
- DOE [DE-AC03-76SF00098]
- Research Computing Support Services (RCSS) of the University of Missouri System
- National Science Foundation of USA [RAPID DMR/CMMT-2028803]
- National Natural Science Foundation of China [12034019]
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The emergence of the new SARS-CoV-2 Omicron variant has worsened the COVID-19 pandemic due to its large number of mutations, particularly in the receptor-binding domain (RBD), making it highly contagious and/or resistant to vaccines. Through molecular dynamics simulations, it has been found that the Omicron variant's RBD binds to ACE2 more efficiently and tightly, resulting in increased infectivity and transmissibility compared to other strains. Some of the RBD mutations have been predicted to affect antibody neutralization either through conformational changes in the spike protein or by altering its surface charge distribution. Other mutations either decrease or increase ACE2 binding.
The emergence of new SARS-CoV-2 Omicron variant of concern (OV) has exacerbated the COVID-19 pandemic because of a large number of mutations in the spike protein, particularly in the receptor-binding domain (RBD), resulting in highly contagious and/or vaccine-resistant strains. Herein, we present a systematic analysis based on detailed molecular dynamics (MD) simulations in order to understand how the OV RBD mutations affect the ACE2 binding. We show that the OV RBD binds to ACE2 more efficiently and tightly predominantly because of strong electrostatic interactions, thereby promoting increased infectivity and transmissibility compared to other strains. Some of the OV RBD mutations are predicted to affect the antibody neutralization either through their role in the S-protein conformational changes, such as S371L, S373P, and S375F, or through changing its surface charge distribution, such as G339D, N440K, T478K, and E484A. Other mutations, such as K417N, G446S, and Y505H, decrease the ACE2 binding, whereas S447N, Q493R, G496S, Q498R, and N501Y tend to increase it.
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