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- W4292755963 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." @default.
- W4292755963 created "2022-08-23" @default.
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- W4292755963 date "2022-09-01" @default.
- W4292755963 modified "2023-09-26" @default.
- W4292755963 title "Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail" @default.
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- W4292755963 doi "https://doi.org/10.1016/j.chom.2022.08.001" @default.
- W4292755963 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36002016" @default.
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