Unexploited viral and host targets for the treatment of human immunodeficiency virus type 1 infection.
To date, all approved drugs for the treatment of infection by human immunodeficiency virus type 1 (HIV-1) target either of two viral enzymes, reverse transcriptase or protease. Drugs targeting different macromolecules could improve upon current shortcomings (ex, drug resistance, metabolism, toxicity, formulation) and provide foundations for novel combination therapies. This review will focus on the two key challenges for any new target--target validation (demonstrating the role in the disease), and target tractability (the likelihood of identifying modulators of that target that have drug-like properties). For this discussion, drug-like molecules are orally active, relatively small organic molecules. All of the virally-encoded proteins (other than reverse transcriptase and protease) and the host targets that have been postulated to be critical for HIV-1 proliferation will be reviewed.
Garvey
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Department of Molecular Biochemistry, GlaxoSmithKline, PO Box 1-3398, Research Triangle Park, North Carolina 27709-3398, USA. epg34374@glaxowellcome.com
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019251:Nucleocapsid / Q000037:antagonists & inhibitors; D015728:Receptors, HIV / Q000187:drug effects; D016914:Ribonuclease H / Q000037:antagonists & inhibitors
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019428:HIV Integrase Inhibitors; D015728:Receptors, HIV; D016914:Ribonuclease H