tetano
Editor, Senior Moderator
Comput Biol Med
. 2021 Jun 12;135:104550.
doi: 10.1016/j.compbiomed.2021.104550. Online ahead of print.
Rational optimization of a human neutralizing antibody of SARS-CoV-2
Jiao Chen[SUP] 1 [/SUP], Fei Wu[SUP] 2 [/SUP], Dan Lin[SUP] 3 [/SUP], Weikang Kong[SUP] 4 [/SUP], Xueting Cai[SUP] 1 [/SUP], Jie Yang[SUP] 1 [/SUP], Xiaoyan Sun[SUP] 5 [/SUP], Peng Cao[SUP] 6 [/SUP]
Affiliations
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
107Y, 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.
. 2021 Jun 12;135:104550.
doi: 10.1016/j.compbiomed.2021.104550. Online ahead of print.
Rational optimization of a human neutralizing antibody of SARS-CoV-2
Jiao Chen[SUP] 1 [/SUP], Fei Wu[SUP] 2 [/SUP], Dan Lin[SUP] 3 [/SUP], Weikang Kong[SUP] 4 [/SUP], Xueting Cai[SUP] 1 [/SUP], Jie Yang[SUP] 1 [/SUP], Xiaoyan Sun[SUP] 5 [/SUP], Peng Cao[SUP] 6 [/SUP]
Affiliations
- PMID: 34147856
- DOI: 10.1016/j.compbiomed.2021.104550
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
107Y, 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.