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Journal of Medicinal Chemistry 2019-Apr

Anti-Zika Activity of a Library of Synthetic Carbohydrate Receptors.

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Kalanidhi Palanichamy
Anjali Joshi
Tugba Mehmetoglu-Gurbuz
M Bravo
Milan Shlain
Frank Schiro
Yasir Naeem
Himanshu Garg
Adam Braunschweig

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概要

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders. Currently, there are no antiviral therapies that have been specifically approved to treat ZIKV, and there is an urgent need to develop effective anti-ZIKV agents. Here, we report anti-ZIKV activity of 16 synthetic carbohydrate receptors (SCRs) that inhibit ZIKV infection in Vero and HeLa cells. Using a ZIKV reporter virus particle-based infection assay, our data demonstrates these SCRs are highly potent with IC50s as low as 0.16 μM and negligible toxicity at several-fold higher concentrations. Time-of-addition studies showed that these SCRs inhibit the early stages of the virus infection, which is consistent with the proposed mode of action, where the SCRs likely inhibit binding between the virus and cell-surface glycans, thereby preventing viral entry into the cells and, as such, this study demonstrates a potential new strategy against ZIKV.

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