9Z1M

Cryo-EM structure of KP.3 spike in complex with Nb9B

Summary for 9Z1M

• Entry DOI: 10.2210/pdb9z1m/pdb
• EMDB information: 73749
• Descriptor: Nanosota-9B, KP.3 spike, 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, entry, viral protein-immune system complex, viral protein/immune system
• Biological source: Vicugna pacos (alpaca); More
• Total number of polymer chains: 6
• Total formula weight: 469402.41

Authors

Ye, G.,Bu, F.,Liu, B.,Li, F. (deposition date: 2025-11-04, release date: 2026-05-13, Last modification date: 2026-06-24)

Primary citation

Bu, F.,Saxena, D.,Turner-Hubbard, H.,Delaney, A.,Batra, L.,Fricke, C.,Moye, S.,Verma, A.,Perlman, S.,Bhandari, J.,Liu, B.,Ye, G.,Zheng, J.,Li, F.
Update and reuse: Structure-guided nanobody evolution against SARS-CoV-2 escape.
Plos Pathog., 22:e1014223-e1014223, 2026

PubMed Abstract: SARS-CoV-2 continues to accumulate spike mutations that erode the efficacy of antibody therapeutics. The Q493E mutation in the spike RBD, present in recent Omicron subvariants, enables escape from many antibodies and nanobodies, including our Nanosota-9A nanobody, which neutralizes Omicron JN.1 (Q493) but not KP.3 (E493). To address this, we applied a structure-guided in vitro evolution strategy to engineer Nanosota-9A, generating Nanosota-9B, which binds the KP.3 RBD with high affinity but shows reduced binding to JN.1 RBD. To regain breadth, we engineered a bispecific nanobody combining Nanosota-9A and -9B, which effectively neutralizes both JN.1 and KP.3 in infection assays. Our results provide proof of concept for an "update and reuse" strategy: applying structure-guided engineering to update and reuse validated nanobodies to overcome variant escape. This strategy offers a practical path to maintain therapeutic coverage as the virus evolves, supporting more efficient use of research resources and faster responses to emerging variants.

PubMed: 42149970
DOI: 10.1371/journal.ppat.1014223

Experimental method

ELECTRON MICROSCOPY (3.06 Å)