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)

8BEV の概要

• エントリーDOI: 10.2210/pdb8bev/pdb
• EMDBエントリー: 15994 15997 16010
• 分子名称: 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)
• 機能のキーワード: sars-cov-2, spike, s protein, hexapro, nanobody, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 301311.51

構造登録者

Lauer, S.,Spahn, C.M.T.,Schwefel, D. (登録日: 2022-10-21, 公開日: 2023-03-08, 最終更新日: 2025-07-16)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (5.92 Å)