TY - JOUR
T1 - Immune Escape Mechanisms of SARS-CoV-2 Delta and Omicron Variants against Two Monoclonal Antibodies That Received Emergency Use Authorization
AU - Xiong, Danyang
AU - Zhao, Xiaoyu
AU - Luo, Song
AU - Cong, Yalong
AU - Zhang, John Z.H.
AU - Duan, Lili
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant nos. 21933010 and 11774207) and the NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We thank the ECNU Public Platform for Innovation 001 for providing supercomputer time.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/7/7
Y1 - 2022/7/7
N2 - Multiple-site mutated SARS-CoV-2 Delta and Omicron variants may trigger immune escape against existing monoclonal antibodies. Here, molecular dynamics simulations combined with the interaction entropy method reveal the escape mechanism of Delta/Omicron variants to Bamlanivimab/Etesevimab. The result shows the significantly reduced binding affinity of the Omicron variant for both antibodies, due to the introduction of positively charged residues that greatly weaken their electrostatic interactions. Meanwhile, significant structural deflection induces fewer atomic contacts and an unstable binding mode. As for the Delta variant, the reduced binding affinity for Bamlanivimab is owing to the alienation of the receptor-binding domain to the main part of this antibody, and the binding mode of the Delta variant to Etesevimab is similar to that of the wild type, suggesting that Etesevimab could still be effective against the Delta variant. We hope this work will provide timely theoretical insights into developing antibodies to prevalent and possible future variants of SARS-CoV-2.
AB - Multiple-site mutated SARS-CoV-2 Delta and Omicron variants may trigger immune escape against existing monoclonal antibodies. Here, molecular dynamics simulations combined with the interaction entropy method reveal the escape mechanism of Delta/Omicron variants to Bamlanivimab/Etesevimab. The result shows the significantly reduced binding affinity of the Omicron variant for both antibodies, due to the introduction of positively charged residues that greatly weaken their electrostatic interactions. Meanwhile, significant structural deflection induces fewer atomic contacts and an unstable binding mode. As for the Delta variant, the reduced binding affinity for Bamlanivimab is owing to the alienation of the receptor-binding domain to the main part of this antibody, and the binding mode of the Delta variant to Etesevimab is similar to that of the wild type, suggesting that Etesevimab could still be effective against the Delta variant. We hope this work will provide timely theoretical insights into developing antibodies to prevalent and possible future variants of SARS-CoV-2.
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U2 - 10.1021/acs.jpclett.2c00912
DO - 10.1021/acs.jpclett.2c00912
M3 - Article
C2 - 35758899
AN - SCOPUS:85134361301
SN - 1948-7185
VL - 13
SP - 6064
EP - 6073
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 26
ER -