7X3C

Cryo-EM structure of Coxsackievirus B1 muture virion in complex with nAbs 8A10 and 5F5 (CVB1-M:8A10:5F5)

7X3C の概要

• エントリーDOI: 10.2210/pdb7x3c/pdb
• EMDBエントリー: 32983
• 分子名称: 8A10 light chain, 8A10 heavy chain, Virion protein 1, ... (9 entities in total)
• 機能のキーワード: coxsackievirus b1, neutralizing antibody, cryo-em, virus
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 144393.64

構造登録者

Zheng, Q.,Zhu, R.,Sun, H.,Cheng, T.,Li, S.,Xia, N. (登録日: 2022-02-28, 公開日: 2022-09-28)

主引用文献

Zheng, Q.,Zhu, R.,Yin, Z.,Xu, L.,Sun, H.,Yu, H.,Wu, Y.,Jiang, Y.,Huang, Q.,Huang, Y.,Zhang, D.,Liu, L.,Yang, H.,He, M.,Zhou, Z.,Jiang, Y.,Chen, Z.,Zhao, H.,Que, Y.,Kong, Z.,Zhou, L.,Li, T.,Zhang, J.,Luo, W.,Gu, Y.,Cheng, T.,Li, S.,Xia, N.
Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.
Cell Host Microbe, 30:1279-1294.e6, 2022

PubMed Abstract: Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB.

PubMed: 36002016
DOI: 10.1016/j.chom.2022.08.001

実験手法

ELECTRON MICROSCOPY (3.03 Å)