7W1S

Crystal structure of SARS-CoV-2 spike receptor-binding domain in complex with neutralizing nanobody Nb-007

7W1S の概要

• エントリーDOI: 10.2210/pdb7w1s/pdb
• 分子名称: Spike protein S1, Nanobody Nb-007 (3 entities in total)
• 機能のキーワード: viral protein/immune system, viral protein-immune system complex
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37621.24

構造登録者

Yang, J.,Lin, S.,Sun, H.L.,Lu, G.W. (登録日: 2021-11-20, 公開日: 2022-06-29, 最終更新日: 2024-10-16)

主引用文献

Yang, J.,Lin, S.,Sun, H.,Chen, Z.,Yang, F.,Lin, X.,Guo, L.,Wang, L.,Wen, A.,Zhang, X.,Dai, Y.,He, B.,Cao, Y.,Dong, H.,Liu, X.,Chen, B.,Li, J.,Zhao, Q.,Lu, G.
A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding.
Front Immunol, 13:820336-820336, 2022

PubMed Abstract: The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

PubMed: 35663966
DOI: 10.3389/fimmu.2022.820336

実験手法

X-RAY DIFFRACTION (1.997 Å)