Molecular Targets of Chemotherapeutic Agents Against the Human Immunodeficiency Virus

There are a multitude of virus-specific proteins and steps in the replicative cycle of the human immunodeficiency virus (HIV) that could act as targets for potential drugs against the acquired immune deficiency syndrome (AIDS). The reverse transcriptase has proven to be the principal if not the sole target for the anti-HIV activity of 2′,3′-dideoxynucleo-side analogues [i.e. 3′-azido-2′, 3′-dideoxythymidine (AZT), 2′,3′-dideoxycytidine (DDC) and 2′, 3′-didehydro-2′, 3′-dideoxy thymidine (D4T)], following intracellular phosphorylation of these nucleoside analogues to their 5′-triphosphates. Sulfated polysaccharides such as heparin, dextran sulfate and pentosan polysulfate block virus adsorption to the outer cell membrane, which implies that these compounds do not have to be taken up by the cells to achieve their anti-HIV activity. Several other viral processes (i.e. uncoating, integration, transcription and assembly) and viral proteins (i.e. protease, tat protein, rev protein and RNase H) have been identified as attractive targets for antiviral chemotherapy, and an intensive search for specific inhibitors of these functions continues.