7X3D

Cryo-EM structure of Coxsackievirus B1 mature virion in complex with nAb 9A3 (CVB1-M:9A3)

Summary for 7X3D

• Entry DOI: 10.2210/pdb7x3d/pdb
• EMDB information: 32984
• Descriptor: Virion protein 1, VP2, VP3, ... (7 entities in total)
• Functional Keywords: coxsackievirus b1, neutralizing antiboy, cryo-em, virus
• Biological source: Coxsackievirus B1; More
• Total number of polymer chains: 6
• Total formula weight: 119640.23

Authors

Zheng, Q.,Zhu, R.,Sun, H.,Cheng, T.,Li, S.,Xia, N. (deposition date: 2022-02-28, release date: 2022-09-28, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.48 Å)