RECENT ADVANCES IN ANTIVIRAL RESEARCH - IDENTIFICATION OF INHIBITORS OF THE HERPESVIRUS PROTEASES

Major advances have been reported in the last two years regarding the molecular biology and structural properties of the herpesvirus proteas es. X-ray diffraction studies have enabled several groups to solve the structure of the human cytomegalovirus protease. Fluorescence-based s ubstrate assays have also been recently reported. These substrates exh ibit sufficient kinetic and sensitivity properties to enable high-thro ughput screening efforts dedicated toward the discovery of protease in hibitors. Three classes of inhibitors have been reported recently: non peptidic aryl trifluoromethylketones; alternate substrate inhibitors ( benzoxazinones/azalactones); and thiol-modifying inhibitors. The thiol -modifying class offers a unique opportunity to discover inhibitors sp ecific to the human cytomegalovirus protease, as this protease require s reduced cysteine residues for its enzymatic activity. (C) Current Bi ology Ltd ISSN 1367-5931.