Interaction analysis of SARS-CoV-2 omicron BA1 and BA2 of RBD with fifty monoclonal antibodies: Molecular dynamics approach

• Published in: Journal of molecular graphics & modelling Vol. 128; p. 108719
• Main Authors: Sandhya, K.S., Kishore, Arsha A., Unni, Arun, Sunitha, P., Sajithra, C.V., Nair, Achuthsankar S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2024
• Subjects: Antibodies; Antibodies, Monoclonal; COVID-19; CR3022; Humans; Molecular docking; Molecular Dynamics Simulation; Molecular dynamics simulations; SARS-CoV-2; Antibodies; SARS-CoV-2; Molecular dynamics simulations; CR3022; Molecular docking
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2024.108719

This report provides detailed insights into the interaction of fifty monoclonal antibodies with two recent Omicron variants, BA1 and BA2. It has been observed that numerous mutations in the receptor binding domain (RBD) result in significant structural changes in Omicron, enhancing its ability to mediate viral infections compared to other variants of concern. The following antibodies, namely JX3S304, 7KMG, 7CH4, 7BELCOVOX45, 7CDJ, 7C01, 7JX3S2H14, 6XCA, 7CDI, 7JMO, 7B3O, 6ZER, 6XC7CR3022, JX3S309, 6XC7CC123, 7CM4, 7KMI, 7L7EAZD8895, exhibit a superior binding affinity towards the Spike when compared to the reference CR3022. Four best-docked systems were subjected to further testing through molecular dynamics (MD) simulations. The MM/GBSA free energy for the top-scored complexes of BA1 variant are BA1_JX3S3O4, BA1_7KMI, BA1_7CH4, and BA1_7KMG, with respective values of −56.120 kcal/mol, −41.30 kcal/mol, −17.546 kcal/mol, and −8.527 kcal/mol; and of BA2 variant are BA2_JX3S3O4, BA2_7CM4, BA2_KMG, and BA2_7CH4, with respective values of −40.903 kcal/mol, −23.416 kcal/mol, −17.350 kcal/mol, and −5.460 kcal/mol. Detailed structural/energetic parameters, principal component analysis, and free energy landscape (FEL) studies reveal a significant decrease in antibody resistance due to the disappearance of numerous hydrogen bond interactions and various metastable states. We believe that these crucial mechanistic insights will contribute to breakthroughs in SARS-CoV-2 research.
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•Molecular dynamics simulations of BA1 and BA2 spike with fifty antibodies have been conducted.•The binding ability of Omicron BA2 is less compared to Omicron BA1.•Omicron BA2 and BA1 retain some binding similarities with CR3022, mutations cause the disappearance of many interactions with most of the antibodies.•Omicron BA1 and BA2 display strong interaction with 23JX3SO4 and 7CM4 than with CR3022.•These antibodies could be useful for the further in vitro and in vio studies.