Abstract

The human immunodeficiency virus type 1 (HIV-1) gp120 and gp41 envelope proteins play essential roles in orchestrating the sequential, multitiered viral entry process. This review discusses antiviral agents that target several key functional areas of gp120: the CD4 and co-receptor binding sites, the V3 loop and specific carbohydrate moieties. These regions represent promising antiviral targets, and significant progress towards the development of novel entry inhibitors has been made in recent years. Importantly, an orally available, small-molecule attachment inhibitor (BMS-488043) and a fusion protein (PRO-542), both targeting the conserved CD4 binding pocket of gp120, have demonstrated clinical efficacy in humans, which validated gp120 as a viable antiviral target. The development of microbicides targeting gp120 to prevent sexual HIV transmission is also discussed.

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