8BEV

Cryo-EM structure of SARS-CoV-2 spike (HexaPro variant) in complex with nanobody W25 (map 3, focus refinement on RBD, W25 and adjacent NTD)

Summary for 8BEV

• Entry DOI: 10.2210/pdb8bev/pdb
• EMDB information: 15994 15997 16010
• Descriptor: Spike glycoprotein, immunoglobulin mu heavy chain, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: sars-cov-2, spike, s protein, hexapro, nanobody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 301311.51

Authors

Lauer, S.,Spahn, C.M.T.,Schwefel, D. (deposition date: 2022-10-21, release date: 2023-03-08, Last modification date: 2025-07-16)

Primary citation

Modhiran, N.,Lauer, S.M.,Amarilla, A.A.,Hewins, P.,Lopes van den Broek, S.I.,Low, Y.S.,Thakur, N.,Liang, B.,Nieto, G.V.,Jung, J.,Paramitha, D.,Isaacs, A.,Sng, J.D.J.,Song, D.,Jorgensen, J.T.,Cheuquemilla, Y.,Burger, J.,Andersen, I.V.,Himelreichs, J.,Jara, R.,MacLoughlin, R.,Miranda-Chacon, Z.,Chana-Cuevas, P.,Kramer, V.,Spahn, C.,Mielke, T.,Khromykh, A.A.,Munro, T.,Jones, M.L.,Young, P.R.,Chappell, K.,Bailey, D.,Kjaer, A.,Herth, M.M.,Jurado, K.A.,Schwefel, D.,Rojas-Fernandez, A.,Watterson, D.
A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants.
Iscience, 26:107085-107085, 2023

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

PubMed: 37361875
DOI: 10.1016/j.isci.2023.107085

Experimental method

ELECTRON MICROSCOPY (5.92 Å)