7x42

Cryo-EM structure of Coxsackievirus B1 pre-A-particle in complex with nAb 8A10 (classified from CVB1 mature virion in complex with 8A10 and 2E6)

spinqualitylabelsall models 7x42, resolution 3.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x42 is a 6 chain structure with sequence from Coxsackievirus B1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.88Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. 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. 2022 Sep 14;30(9):1279-1294.e6. doi: , 10.1016/j.chom.2022.08.001. Epub 2022 Aug 23. PMID:36002016 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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