The HIV-1 protease as a therapeutic target for AIDS.
HIV produces a small , dimeric aspartyl protease which specifically cleaves the polyprotein precursors encoding the structural proteins and enzymes of the virus. This proteolytic activity is absolutely required for the production of mature, infectious virions and is therefore an attractive target for therapeutic intervention. This review summarizes the strategies and multidisciplinary efforts that have been applied to date to the identification of specific inhibitors of this critical viral enzyme. These inhibitors include rationally designed peptide substrate analogs, compounds conceived from tertiary structure information on the enzyme and natural products. Future directions in the discovery and development of HIV-1 protease inhibitors are also discussed.
Debouck
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Department of Molecular Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D005544:Forecasting; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D016333:HIV Protease