HIV-1 integrase: a target for new AIDS chemotherapeutics.
Since the beginning of the HIV epidemic almost 70 million people have been infected with HIV. It is estimated that 42 million people are currently living with HIV/AIDS. The spread of HIV continues throughout the world and current estimates indicate that in 2002, 5 million people were newly infected with HIV and 3 million people died. Current treatments employ a combination of therapeutic agents that target the viral reverse transcriptase and protease enzymes and viral entry. However the clinical benefit of these agents is often limited due to issues of regimen compliance, significant side effects, and the emergence of viral strains that are drug resistant. The introduction of novel agents that interfere with alternate stages in the viral life cycle represent potential solutions to these problems. The integration of the HIV genome into the cellular chromosome, a process catalyzed by the viral enzyme integrase, has been shown to be essential for viral replication. Since HIV integrase has no direct cellular counterpart it presents itself as an attractive target for therapeutic intervention. This review summarizes recent and promising developments both in the HIV integrase field and the global quest for therapeutically useful inhibitors of HIV integrase.
Anthony
Neville J
NJ
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. neville_anthony@merck.com
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019427:HIV Integrase / Q000187:drug effects / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase