Structural and functional analysis of VYD222: a broadly neutralizing antibody against SARS-CoV-2 variants.

ABSTRACT: Extensive mutations in SARS-CoV-2 spike protein have rendered most therapeutic monoclonal antibodies (mAbs) ineffective. However, here we describe VYD222 (pemivibart), a human mAb re-engineered from ADG20 (adintrevimab), which maintains potency despite substantial virus evolution. VYD222 received FDA Emergency Use Authorization for pre-exposure prophylaxis of COVID-19 in certain immunocompromised adults and adolescents. Here we show potent neutralization of this antibody against a broad range of emerging variants, including Omicron KP.3 and KP.3.1.1. X-ray crystal structures of VYD222 complexed with the receptor-binding domains of prototype SARS-CoV-2 and Omicron BA.5 demonstrate the binding epitope spans from the receptor binding site to the conserved CR3022 site. Notably, many of the mat

SUBMITTER: Yuan M 

PROVIDER: S-EPMC12407960 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature