Structure and dynamics of the interaction of Delta and Omicron BA.1 SARS-CoV-2 variants with REGN10987 Fab reveal mechanism of antibody action.

ABSTRACT: Study of mechanisms by which antibodies recognize different viral strains is necessary for the development of new drugs and vaccines to treat COVID-19 and other infections. Here, we report 2.5 Å cryo-EM structure of the SARS-CoV-2 Delta trimeric S-protein in complex with Fab of the recombinant analog of REGN10987 neutralizing antibody. S-protein adopts "two RBD-down and one RBD-up" conformation. Fab interacts with RBDs in both conformations, blocking the recognition of angiotensin converting enzyme-2. Three-dimensional variability analysis reveals high mobility of the RBD/Fab regions. Interaction of REGN10987 with Wuhan, Delta, Omicron BA.1, and mutated variants of RBDs is analyzed by microscale thermophoresis, molecular dynamics simulations, and ΔG calculations with umbrella sampling and

SUBMITTER: Lyukmanova EN 

PROVIDER: S-EPMC11668877 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature