Antibody escape of SARS-CoV-2 variants of concern on receptor-binding domain: A computational approach

The receptor-binding domain (RBD) of the spike protein is a critical functional component responsible for binding between the SARS-CoV-2 and the ACE2 receptor, as well as monoclonal antibodies. This research focuses on evaluating the ability of SARS-CoV-2 variants to reduce or evade neutralizing antibody responses. The RBD structures of wild type, Delta, and Omicron structures along with nine RBD-directed antibodies downloaded from the Protein Data Bank were subjected to docking simulations via the HADDOCK 2.4 server to calculate Haddock score, binding affinity (ΔG) and dissociation constant (K_d). The resulting complexes underwent molecular dynamics simulations for 100 ns using GROMACS, and the binding free energy was calculated using gmx_MMPBSA. The findings indicated that the L452R and T478K mutations in Delta, as well as the K417N, E484A, S477N, and Q493R mutations in Omicron, were predicted to be pivotal factors in the interaction with antibodies. Omicron exhibited a greater potential for immune evasion compared to Delta. Notably, the Sotrovimab antibody demonstrated robust interactions with both variants. Etesevimab exhibited strong binding with Delta but displayed a weaker connection with Omicron. Therefore, Sotrovimab and Etesevimab remain promising candidates for in vitro and in vivo testing against SARS-CoV-2 variants.