Inhibition of HIV-1 integrase by small molecules: the potential for a new class of AIDS chemotherapeutics.
HIV-1 integrase, one of three constitutive viral enzymes required for replication, is an attractive target for chemotherapeutic intervention in the treatment of AIDS. Unlike the retroviral reverse transcriptase and protease enzymes, successful drug candidates based on the inhibition of integrase have yet to emerge despite the multitude of laboratories working on the problem. In vitro inhibition of integrase in the laboratory has not always led to antiviral activity in cell culture. Indeed, most compounds found from broad screening efforts have fallen into this category. Only recently have compounds that inhibit enzymatic function as well as exhibiting an antiviral effect as a result been discovered. The reasons why certain structural classes of compounds fail to have antiviral activity are only beginning to be understood. In the last two years a new class of compounds has emerged that do produce potent inhibition of viral growth in cell culture. Further work in this area may yet produce clinically useful antiviral agents.
Young
S D
SD
Department of Medicinal Chemistry, Merck Research Laboratories, WP14-3, West Point, PA 19486, USA. steve_young@merck.com
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000201:enzymology*; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019427:HIV Integrase