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Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.

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
Cell Host Microbe 30 1279-1294.e6 (2022)
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Cited: 1 times
EuropePMC logo PMID: 36002016

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.

Articles citing this publication (1)

  1. A counterintuitive antibody cocktail disrupts coxsackievirus. Zost SJ, Vogt MR. Cell Host Microbe 30 1194-1195 (2022)


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