Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge with Glu329 of hACE2, which resulted in greater electrostatic complementarity, and created a weak salt bridge with Asp442 of RBD. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. The results show consistent with the previous experimental conclusion and clarify the structural mechanism under affinity changes. Our methods will offer guidance on the assessment of the infection efficiency and antigenicity effect of continuing mutations in SARS-CoV-2.
【저자키워드】 neutralizing antibody, SARS-CoV-2, molecular dynamics, binding free energy, N439K, 【초록키워드】 COVID-19, coronavirus disease, ACE2, coronavirus, Mutation, neutralization, mutations, Infection, Diagnosis, hACE2, Molecular dynamics simulation, Receptor binding domain, Epidemic, Surveillance, outbreak, RBD, Neutralizing, REGN10987, antigenicity, protein-protein interaction, Guidance, mechanism, neutralizing monoclonal antibody, Analysis, Efficiency, changes, acute respiratory syndrome, enzyme, wild-type, RBD region, higher affinity, offer, Effect, Salt Bridge, greater, addition, electrostatic, the SARS-CoV-2, 【제목키워드】 spike, Dynamics, Simulation,