Compared to C8, the binding of EDE2 A11 extremely relies on the variable 150 loop in which glycosylation is not always present. al.et al. et al. et al.et al. et al.et al.et al.et al.(Fibriansah and Lok 2016; Zhaoet al. et al.et al.et al.et al.et al.et al.et al. et al.and (Barba-Spaethet al.et al. assays have shown that this ADE phenomenon occurred between ZIKV and DENV (Liet al.et al. et al. et al.et al.et al.et al.et al. et al.et al.and provide safety in ZIKV lethal challenge models et al.et al.et al.of domain II and the fusion loop main chain. The absence of the N67 glycan in ZIKV showed that these contacts were not essential for binding. Compared to C8, the binding of EDE2 A11 extremely relies on the variable 150 loop in which glycosylation is not always present. This is clearly a drawback of EDE2 mAbs as shown by their poor affinity and their strong induction of ADE. Because of these reasons, the epitopes of EDE1 mAbs are more suitable than that of EDE2 mAbs for development of the potent epitope-focused vaccines for ZIKV and DENV super serogroup (Barba-Spaethet al.et al.et al.et al.et al.et al.et al.et al. /em 2016). Open in a separate windows Fig.?3 A The Z20 Fab binds to the central region of sE dimer from the top surface. The PDB only can output the monomeric E complexes with Fab. B The Decursin Z3L1 Fab binds to the distal region of the sE dimer from the top surface. The PDB only can output the monomeric E complexes with Fab. C The Z23 Fab binds to DIII of one envelope protein monomer and may cross-react with two envelope protein dimers within the virion surface. Due to the low resolution of complex, it could not display more details. Potential customers for Development of Neutralizing Antibodies against ZIKV Based on More Refined Structural Info Even after all the studies that have been carried out to map different epitopes in ZIKV, still a lot of areas remain elusive. Structure-guided analysis, primarily using cryo-EM solitary particle methods as well as computational simulations, will be very helpful for ideal epitope selection as a key step for executive fresh neutralizing antibodies against the computer virus. Structural vaccinology, in which protein structure info is used to design immunogens, has promise to provide fresh vaccines against hard focuses on, as ZIKV. Within the last few years, several key advances possess allowed for better and better resolution within the cryo-EM field: 1st, a new type of video camera (direct electron detectors) has been introduced, which allows for much better signal detection; and second, more computing power coupled with new algorithms for processing images has allowed researchers to tease more information out of existing electron microscopic images. For the first time, it is possible to acquire near-atomic resolution information from cryo-EM. This technology will be key to map different epitopes for new mAbs targeting Tead4 ZIKV. Our main goal will be to use this structural information to optimize a vaccine design approach. However, electron microscopists know that single particle cryo-EM is not the only way to understand antibodyCantigen interactions. We know that flexibility is not good for cryo-EM. Some antibodyCantigen binding can show some degree of flexibility. In those cases, those epitopes cannot be resolved by EM. Using computational simulations as well as small angle neutron scattering (SANS) will be very helpful to resolve those flexible areas. Our plan is to combine all these technologies: Cryo-EM, SANS as well Decursin as computational modeling to develop a better vaccine development approach against ZIKV. Decursin Acknowledgements We are thankful to The Core Facility and Technical.