9CO9

Local refinement of JN.1 spike/Nanosota-9 complex

Summary for 9CO9

• Entry DOI: 10.2210/pdb9co9/pdb
• EMDB information: 45774
• Descriptor: Spike glycoprotein, Nanosota-9 (2 entities in total)
• Functional Keywords: spike, nanobody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 309284.76

Authors

Ye, G.,Bu, F.,Liu, B.,Li, F. (deposition date: 2024-07-16, release date: 2024-11-20, Last modification date: 2024-12-11)

Primary citation

Ye, G.,Bu, F.,Saxena, D.,Turner-Hubbard, H.,Herbst, M.,Spiller, B.,Wadzinski, B.E.,Du, L.,Liu, B.,Zheng, J.,Li, F.
Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.
Plos Pathog., 20:e1012726-e1012726, 2024

PubMed Abstract: Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.

PubMed: 39591462
DOI: 10.1371/journal.ppat.1012726

Experimental method

ELECTRON MICROSCOPY (3.44 Å)