8UG9

XBB.1.5 spike/Nb5 complex

Summary for 8UG9

• Entry DOI: 10.2210/pdb8ug9/pdb
• EMDB information: 42218
• Descriptor: Nanosota-5, Spike glycoprotein, 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/immune system
• Biological source: Vicugna pacos (alpaca); More
• Total number of polymer chains: 6
• Total formula weight: 467252.48

Authors

Ye, G.,Bu, F.,Liu, B.,Li, F. (deposition date: 2023-10-05, release date: 2024-08-28, Last modification date: 2024-11-20)

Primary citation

Ye, G.,Bu, F.,Pan, R.,Mendoza, A.,Saxena, D.,Zheng, J.,Perlman, S.,Liu, B.,Li, F.
Dual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants.
Plos Pathog., 20:e1012493-e1012493, 2024

PubMed Abstract: Grasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either neutralize, have no effect on, or enhance viral entry into cells. Here, we used nanobodies (single-domain antibodies) as probes to investigate a unique epitope on the SARS-CoV-2 spike protein, located outside the protein's receptor-binding domain. Nanobody binding to this epitope enhances the cell entry of prototypic SARS-CoV-2, while neutralizing the cell entry of SARS-CoV-2 Omicron variant. Moreover, nanobody binding to this epitope promotes both receptor binding activity and post-attachment activity of prototypic spike, explaining the enhanced viral entry. The opposite occurs with Omicron spike, explaining the neutralized viral entry. This study reveals a unique epitope that can both enhance and neutralize viral entry across distinct viral variants, suggesting that epitopes may vary their roles depending on the viral context. Consequently, antibody therapies should be assessed across different viral variants to confirm their efficacy and safety.

PubMed: 39236072
DOI: 10.1371/journal.ppat.1012493

Experimental method

ELECTRON MICROSCOPY (3.49 Å)