EMD-32970

Single-particle
3.69 Å
EMD-32970 Deposition: 26/02/2022
Map released: 28/09/2022
Last modified: 05/10/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-32970

Cryo-EM structure of Coxsackievirus B1 mature virion in complex with nAb 8A10 (CVB1-M:8A10)

EMD-32970

Single-particle
3.69 Å
EMD-32970 Deposition: 26/02/2022
Map released: 28/09/2022
Last modified: 05/10/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Coxsackievirus B1, Mus musculus
Sample: Cryo-EM structure of Coxsackievirus B1 mature virion in complex with nAb 8A10 (CVB1-M:8A10)
Fitted models: 7x2t (Avg. Q-score: 0.531)

Deposition Authors: Zheng Q, Zhu R, Sun H, Cheng T, Li S, Xia N
Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.
PUBMED: 36002016
DOI: doi:10.1016/j.chom.2022.08.001
ISSN: 1934-6069
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.