Binding Interactions between Receptor-Binding Domain of Spike Protein and Human Angiotensin Converting Enzyme-2 in Omicron Variant.
J Phys Chem Lett
; 13(17): 3915-3921, 2022 May 05.
Article
in English
| MEDLINE | ID: covidwho-1815471
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Prognostic study
/
Systematic review/Meta Analysis
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2022
Document Type:
Article
Affiliation country:
Acs.jpclett.2c00423
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