期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 9, 期 -, 页码 6389-6399出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S94207
关键词
flavivirus protease; small molecule optimization; covalent inhibitor; active site binding; pyrazole ester derivatives
资金
- Agency for Science, Technology and Research (A*STAR), Singapore
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据