Comput Biol Med . Rational optimization of a human neutralizing antibody of SARS-CoV-2

[tetano]

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 ¹ , Fei Wu ² , Dan Lin ³ , Weikang Kong ⁴ , Xueting Cai ¹ , Jie Yang ¹ , Xiaoyan Sun ⁵ , Peng Cao ⁶



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: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.