8JYS

SARS-CoV-2 Spike RBD (dimer) in complex with two 2S-1244 nanobodies

8JYS の概要

• エントリーDOI: 10.2210/pdb8jys/pdb
• EMDBエントリー: 36730
• 分子名称: IBT-CoV144 nanobody, Spike protein S1 (2 entities in total)
• 機能のキーワード: spike, nanobody, dimer, local, viral protein
• 由来する生物種: Camelus bactrianus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75416.53

構造登録者

Yang, Y.,Zhang, C.H. (登録日: 2023-07-03, 公開日: 2024-06-12, 最終更新日: 2025-07-23)

主引用文献

Yang, Y.,Zhang, J.,Zhang, S.,Zhang, C.,Shen, C.,Song, S.,Wang, Y.,Peng, Y.,Gong, X.,Dai, J.,Xie, C.,Khrustaleva, T.A.,Khrustalev, V.V.,Huo, Y.,Lu, D.,Yao, D.,Zhao, J.,Liu, Y.,Lu, H.
A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.
Exploration (Beijing), 4:20230086-20230086, 2024

PubMed Abstract: The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT-CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo-EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the "up" state and bound by six VHHs. IBT-CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT-CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next-generation vaccines.

PubMed: 38939869
DOI: 10.1002/EXP.20230086

実験手法

ELECTRON MICROSCOPY (4.5 Å)