Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

ABSTRACT: Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody

SUBMITTER: Yao H 

PROVIDER: S-EPMC7705443 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature