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

✍ Scribed by Daniel L Flynn; Norman A Abood; Barry C Holwerda

• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 850 KB
• Volume: 1
• Category: Article
• ISSN: 1367-5931
• DOI: 10.1016/s1367-5931(97)80009-9

✦ Synopsis

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.