Structure-guided in vitro evolution of nanobodies targeting new viral variants

• DOI: 10.1371/journal.ppat.1012600
• Publication Date: 2024-09-26T17:45:37Z
• Authors: Gang Ye; Fan Bu; Ruangang Pan; Alise Mendoza; Ge Yang; Benjamin Spiller; Brian E. Wadzinski; Lanying Du; Stanley Perlman; Bin Liu; Fang Li
• Keywords: Viral evolution

A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies—single-domain antibodies derived from camelids—can be rapidly re-engineered to combat new viral strains through structure-guided vitro evolution. Specifically, for mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select variants effectively bind mutated target a phage display library. As proof concept, used this approach adapt Nanosota-3, originally identified receptor-binding domain (RBD) early Omicron subvariants, making it highly effective against recent subvariants. Remarkably, adaptation process can completed less than two weeks, allowing drug development keep pace and provide timely protection humans.