Integrating immune library probing with structure-based computational design to develop potent neutralizing nanobodies against emerging SARS-CoV-2 variants.

ABSTRACT: To generate antibodies (Abs) against SARS-CoV-2 emerging variants, we integrated multiple tools and engineered molecules with excellent neutralizing breadth and potency. Initially, the screening of an immune library identified a nanobody (Nb), termed Nb4, specific to the receptor-binding domain (RBD) of the Omicron BA.1 variant. A Nb4-derived heavy chain antibody (hcAb4) recognized the spike (S) of the Wuhan, Beta, Delta, Omicron BA.1, and BA.5 SARS-CoV-2 variants. A high-resolution crystal structure of the Nb4 variable (VHH) domain in complex with the SARS-CoV-2 RBD (Wuhan) defined the Nb4 binding mode and interface. The Nb4 VHH domain grasped the RBD and covered most of its outer face, including the core and the receptor-binding motif (RBM), which was consistent with hcAb4 blocking RBD b

SUBMITTER: Cerdan L 

PROVIDER: S-EPMC12064060 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature