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Updated: Mar 28, 2026

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Identification of covalent active site inhibitors of dengue virus protease
Xiaoying Koh-Stenta1, Joma Joy1, Si Fang Wang1
1Experimental Therapeutics Centre, Agency for Science, Technology and Research (ASTAR), Singapore.
Abstract:
Dengue virus (DENV) protease is an attractive target for drug development; however, no compounds have reached clinical development to date. In this study, we utilized a potent West Nile virus protease inhibitor of the pyrazole ester derivative class as a chemical starting point for DENV protease drug development. Compound potency and selectivity for DENV protease were improved through structure-guided small molecule optimization, and protease-inhibitor binding interactions were validated biophysically using nuclear magnetic resonance. Our work strongly suggests that this class of compounds inhibits flavivirus protease through targeted covalent modification of active site serine, contrary to an allosteric binding mechanism as previously described.
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