9C6Y

Crystal structure of SARS-CoV-2 XBB.1.5 RBD bound to COV2-3906 Fab

Summary for 9C6Y

• Entry DOI: 10.2210/pdb9c6y/pdb
• Descriptor: Heavy chain of COV2-3906 Fab, Light chain of COV2-3906 Fab, Spike protein S2', ... (10 entities in total)
• Functional Keywords: coronavirus, antibody, fab, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 146099.36

Authors

Buchman, C.D.,Crowe, J.E. (deposition date: 2024-06-10, release date: 2025-10-08, Last modification date: 2026-04-22)

Primary citation

Zost, S.J.,Suryadevara, N.,Williamson, L.E.,Scheaffer, S.M.,Binshtein, E.,Buchman, C.D.,Johnson, N.V.,Catanzaro, N.J.,Ravera, S.,Chapman, N.S.,Myers, L.,Ramamohan, A.R.,Handal, L.S.,Nguyen, D.C.,Trivette, A.,Martinez, J.R.,Villalobos, E.,Rutherford, S.A.,Eun-Hyung Lee, F.,Schafer, A.,Baric, R.S.,McLellan, J.S.,Diamond, M.S.,Carnahan, R.H.,Crowe Jr., J.E.
Epitope-focused discovery of SARS-CoV-2 antibodies that potently neutralize Omicron variants.
Nat Microbiol, 11:1113-1132, 2026

PubMed Abstract: The emergence of SARS-CoV-2 Omicron variants has led to viral escape from many clinically approved monoclonal antibodies (mAbs) due to rapid evolution of the receptor-binding domain (RBD). Co-circulation of SARS-CoV-2 variants with unique sets of antigenic substitutions has further complicated therapeutic mAb discovery. New approaches are needed to rapidly discover and characterize mAbs with preferred specificity and functional characteristics. Here we describe and perform epitope-focused mAb discovery using glycan-masked antigens. We isolated and expressed a panel of 303 mAbs, some of which potently neutralize divergent Omicron subvariants by targeting the class 3 antigenic site on SARS-CoV-2 RBD. Epitope mapping of these antibodies revealed a spectrum of cross-reactivity and differential recognition of the class 3 site, validating the utility of this enrichment approach for targeted mAb discovery. Together, this work rationally designs glycan-masked engineered RBDs and uses them to isolate mAbs that potently neutralize antigenically divergent SARS-CoV-2 variants.

PubMed: 41820555
DOI: 10.1038/s41564-026-02282-x

Experimental method

X-RAY DIFFRACTION (2.68 Å)