Herpesvirus proteases: targets for novel antiviral drugs.
Herpesvirus proteases have emerged as targets for the development of novel antiviral drugs. These enzymes, which are necessary for the replication of all herpesviruses, are serine proteases, but possess a unique structure as revealed by solution of the crystal structure of human cytomegalovirus protease. Many of the biochemical properties of these enzymes are now explained by the structure. Conventional serine protease inhibitors are not potent inhibitors of these enzymes and therefore the search for potent inhibitors possessing necessary features of an effective antiviral will require novel approaches. The three-dimensional structure serves as a milestone for continued endeavors towards this goal.
Holwerda
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BC
Searle Research and Development, St. Louis, MO 63198, USA. bcholw@ccmail.monsanto.com
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D003587:Cytomegalovirus / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D006564:Herpesviridae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013379:Substrate Specificity
D000998:Antiviral Agents; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases