9ATO

XBB.1.5 spike/Nanosota-3C complex

Summary for 9ATO

• Entry DOI: 10.2210/pdb9ato/pdb
• EMDB information: 43831
• Descriptor: Spike glycoprotein, Nanosota-3C, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, xbb.1.5, nanobody, viral protein-immune system complex, viral protein, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 463170.79

Authors

Ye, G.,Bu, F.,Liu, B.,Li, F. (deposition date: 2024-02-27, release date: 2024-09-18, Last modification date: 2025-04-02)

Primary citation

Ye, G.,Bu, F.,Pan, R.,Mendoza, A.,Yang, G.,Spiller, B.,Wadzinski, B.E.,Du, L.,Perlman, S.,Liu, B.,Li, F.
Structure-guided in vitro evolution of nanobodies targeting new viral variants.
Plos Pathog., 20:e1012600-e1012600, 2024

PubMed Abstract: 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 in vitro evolution. Specifically, for viral mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select nanobody variants that effectively bind to the mutated viral target from a phage display library. As a proof of concept, we used this approach to adapt Nanosota-3, a nanobody originally identified to target the receptor-binding domain (RBD) of early Omicron subvariants, making it highly effective against recent Omicron subvariants. Remarkably, this adaptation process can be completed in less than two weeks, allowing drug development to keep pace with viral evolution and provide timely protection to humans.

PubMed: 39325826
DOI: 10.1371/journal.ppat.1012600

Experimental method

ELECTRON MICROSCOPY (3.2 Å)