9PSN

Crystal structure of SARS-CoV-2 receptor binding domain in complex with antibodies BoWLB-105 and CC12.3

Summary for 9PSN

• Entry DOI: 10.2210/pdb9psn/pdb
• Descriptor: Spike protein S1 receptor binding domain, TRIETHYLENE GLYCOL, TETRAETHYLENE GLYCOL, ... (12 entities in total)
• Functional Keywords: covid-19, sars-cov-2, receptor binding domain, antibody, immune system, immune system-viral protein complex, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 10
• Total formula weight: 238815.34

Authors

Feng, Z.,Wilson, I.A. (deposition date: 2025-07-25, release date: 2026-02-25, Last modification date: 2026-05-27)

Primary citation

Fu, Y.,Feng, Z.,Erickson, S.A.,Halfmann, P.J.,Li, L.,Chervin, J.C.,Troxell, C.A.,Sun, J.,Yasuhara, A.,Changrob, S.,Huang, M.,Zheng, N.Y.,Yuan, M.,Kawaoka, Y.,Wilson, I.A.,Wilson, P.C.
In vivo evolution of antibody CR3022 expands cross-neutralization of SARS-CoV-2 variants and informs pan-sarbecovirus immunity.
Cell Rep, 45:117137-117137, 2026

PubMed Abstract: The epitope that monoclonal CR3022 binds to represents a promising target for broad protection against a wide range of human and zoonotic coronaviruses. We develop a powerful model to evaluate antibody affinity maturation in vivo using immunoglobulin (Ig)-humanized mice that express the predicted germline heavy chain of antibody CR3022. Severe acute respiratory syndrome coronavirus (SARS-CoV)/SARS-CoV-2 sequential immunization leads to the convergent evolution of the germline CR3022 through somatic hypermutation (SHM), resembling the affinity-matured CR3022 from a human but now also adapting to key variants and divergent sarbecoviruses. While simple prime-boost strategies drive CR3022-epitope targeting, an intensive vaccination protocol elicits dominant responses to other epitopes. X-ray crystal structures reveal that SARS-CoV-2-neutralizing CR3022-like antibodies exhibit enhanced affinity by increasing polar and electrostatic interactions. Overall, these findings show that CR3022-like clones can be readily adapted through SHM to increase breadth and potency to sarbecoviruses by relatively minor shifts in affinity with appropriate vaccination strategies.

PubMed: 41865371
DOI: 10.1016/j.celrep.2026.117137

Experimental method

X-RAY DIFFRACTION (2.54 Å)