Molecules, Vol. 24, Pages 1465: Discovery and Computational Analyses of Novel Small Molecule Zika Virus Inhibitors

In this study, an in silico screening of the National Cancer Institute (NCI) diversity set based on ZIKV NS3 helicase was performed using a molecular docking approach. Selected compounds with drug-like properties were subjected to cell-based antiviral assays resulting in the identification of two novel lead compounds (named Compounds 1 and 2). They inhibited ZIKV infection with IC50 values at the micro-molar level (8.5 μM and 15.2 μM, respectively). Binding mode analysis, absolute binding free energy calculation, and structure–activity relationship studies of these two compounds revealed their possible interactions with ZIKV NS3 helicase, suggesting a mechanistic basis for further optimization. These two novel small molecules may represent new leads for the development of inhibitory drugs against ZIKV.

Source: Molecules - April 12, 2019 Category: Chemistry Authors: Siyu Zhu Chaozai Zhang Lina S. Huang Xing-Quan Zhang Yan Xu Xiong Fang Jiao Zhou Meixian Wu Robert T. Schooley Ziwei Huang Jing An Tags: Article Source Type: research