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.
Keywords: Immunodeficiency Virus Type 1 Infection, reverse transcriptase (RT), nucleoside RT inhibitors, VIRAL TARGETS, Integrase, ENV, Gp41, RNASE H, GP120, NUCLEOCAPSID, NONESSENTIAL ACCESSORY PROTEINS