7WHI

The state 2 complex structure of Omicron spike with Bn03 (2-up RBD, 4 nanobodies)

7WHI の概要

• エントリーDOI: 10.2210/pdb7whi/pdb
• EMDBエントリー: 32500
• 分子名称: Spike glycoprotein, Bn03_nano1, Bn03_nano2, ... (4 entities in total)
• 機能のキーワード: omicron, spike, nanobody, viral protein
• 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: 7
• 化学式量合計: 491238.33

構造登録者

Zhan, W.Q.,Zhang, X.,Chen, Z.G.,Sun, L. (登録日: 2021-12-30, 公開日: 2022-05-11, 最終更新日: 2025-07-02)

主引用文献

Li, C.,Zhan, W.,Yang, Z.,Tu, C.,Hu, G.,Zhang, X.,Song, W.,Du, S.,Zhu, Y.,Huang, K.,Kong, Y.,Zhang, M.,Mao, Q.,Gu, X.,Zhang, Y.,Xie, Y.,Deng, Q.,Song, Y.,Chen, Z.,Lu, L.,Jiang, S.,Wu, Y.,Sun, L.,Ying, T.
Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody.
Cell, 185:1389-1401.e18, 2022

PubMed Abstract: The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have been limited by the continuous emergence of viral variants and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.

PubMed: 35344711
DOI: 10.1016/j.cell.2022.03.009

実験手法

ELECTRON MICROSCOPY (2.93 Å)