Recent advances in antiviral research: identification of inhibitors of the herpesvirus proteases

被引:24
|
作者
Flynn, DL
Abood, NA
Holwerda, BC
机构
[1] Searle Res & Dev, Dept Med Chem, St Louis, MO 63167 USA
[2] Searle Res & Dev, Dept Infect Dis Res, St Louis, MO 63198 USA
关键词
D O I
10.1016/S1367-5931(97)80009-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Major advances have been reported in the last two years regarding the molecular biology and structural properties of the herpesvirus proteases. X-ray diffraction studies have enabled several groups to solve the structure of the human cytomegalovirus protease. Fluorescence-based substrate assays have also been recently reported. These substrates exhibit sufficient kinetic and sensitivity properties to enable high-throughput screening efforts dedicated toward the discovery of protease inhibitors. Three classes of inhibitors have been reported recently: nonpeptidic aryl trifluoromethylketones; alternate substrate inhibitors (benzoxazinones/azalactones); and thiol-modifying inhibitors. The thiol-modifying class offers a unique opportunity to discover inhibitors specific to the human cytomegalovirus protease, as this protease requires reduced cysteine residues for its enzymatic activity. (C) Current Biology Ltd ISSN 1367-5931.
引用
收藏
页码:190 / 196
页数:7
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