Abstract
SARS-CoV-2 has caused a worldwide epidemic of coronavirus disease 19 (COVID-19). Antibody drugs present an effective weapon for tens of millions of COVID-19 patients. Antibodies disrupting the interactions between the receptor-binding domain (RBD) of SARS-CoV-2 S protein and the angiotensin converting enzyme 2 (ACE2) effectively block SARS-CoV-2 cell entry into host cells. In order to rapidly develop more potent neutralizing antibodies, we utilized virtual scanning mutageneses and molecular dynamics simulations to optimize the antibody of P2B-2F6 isolated from single B cells of SARS-CoV-2 infected patients. Two potent P2B-2F6 mutants, namely H:V106R and H:V106R/H:P107Y, were found to possess higher binding affinities with the RBD domain of SARS-CoV-2 than others. Polar interactions are preferred near 106 and 107 paratope residues of the heavy chain. The mutations also increase the hydrogen-bonding network formed between the antibody and the RBD. Notably, the optimized antibodies possess potential neutralizing activity against the alarming SARS-CoV-2 variant of N501Y. This study provides insights into structure-based optimization of antibodies with higher affinity to the antigen. We hope that our proposed antibody mutants could contribute to the development of improved therapies against COVID-19.
Keywords: Antibody; COVID-19; Molecular dynamics simulation; SARS-CoV-2; Scanning mutageneses.
【저자키워드】 COVID-19, SARS-CoV-2, antibody, Molecular dynamics simulation, Scanning mutageneses., 【초록키워드】 coronavirus disease, ACE2, coronavirus, therapy, Mutation, S protein, Neutralizing antibodies, antibody, angiotensin converting enzyme 2, SARS-CoV-2 variant, drug, molecular dynamics, molecular dynamics simulations, angiotensin converting enzyme, binding affinity, Molecular dynamics simulation, Antigen, Neutralizing activity, Epidemic, Receptor-binding domain, RBD, N501Y, mutants, mutant, COVID-19 patients, SARS-CoV-2 S protein, Interaction, angiotensin, RBD domain, host cells, hydrogen, binding affinities, heavy chain, SARS-CoV-2 infected patients, enzyme, domain, scanning, higher affinity, polar interactions, effective, single B cells, develop, caused, provide, contribute, the RBD, the receptor-binding domain, disrupting, paratope residue, SARS-CoV-2 cell, single B cell, 【제목키워드】 neutralizing antibody,