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Immune Escape Mechanisms of SARS-CoV-2 Delta and Omicron Variants against Two Monoclonal Antibodies That Received Emergency Use Authorization.

ABSTRACT: 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.

SUBMITTER: Xiong D

PROVIDER: S-EPMC9260724 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Dataset Information

Immune Escape Mechanisms of SARS-CoV-2 Delta and Omicron Variants against Two Monoclonal Antibodies That Received Emergency Use Authorization.

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