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 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.
Flynn
D L
DL
Searle Research and Development, Department of Medicinal Chemistry, 800 N Lindbergh Blvd, St Louis, MO 63167, USA. dlflyn@monsanto.com
Abood
N A
NA
Holwerda
B C
BC
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000627:therapeutic use*; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors