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Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction.

Cell Res.. 2017; 
Li Zhong,Brecher Matthew,Deng Yong-Qiang,Zhang Jing,Sakamuru Srilatha,Liu Binbin,Huang Ruili,Koetzner Cheri A,Allen Christina A,Jones Susan A,Chen Haiying,Zhang Na-Na,Tian Min,Gao Fengshan,Lin Qishan,Banavali Nilesh,Zhou Jia,Boles Nathan,Xia Menghang,Kramer Laura D,Qin Cheng-Feng,Li Hon
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Catalog Antibody .... (Genscript) and anti-GST antibodies (GE HealthCare). (B) Dose-dependent inhibition of NS2B-NS3 interactions.... with 0.05% CHAPS, and subjected to western blot analysis using anti-FLAG antibody (A00170-40, Genscript Get A Quote

摘要

Recent outbreaks of Zika virus (ZIKV) highlight an urgent need for therapeutics. The protease complex NS2B-NS3 plays essential roles during flaviviral polyprotein processing, and thus represents an attractive drug target. Here, we developed a split luciferase complementation-based high-throughput screening assay to identify orthosteric inhibitors that directly target flavivirus NS2B-NS3 interactions. By screening a total of 2 816 approved and investigational drugs, we identified three potent candidates, temoporfin, niclosamide, and nitazoxanide, as flavivirus NS2B-NS3 interaction inhibitors with nanomolar potencies. Significantly, the most potent compound, temoporfin, not only inhibited ZIKV... More

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