The envelope glycoprotein complex (Env) is responsible for entry of the human immunodeficiency virus type 1 (HIV-1) into cells by mediating attachment to target cells and subsequent membrane fusion. Env consists of three gp120 subunits that mediate receptor and co-receptor attachment and three gp41 subunits responsible for membrane fusion. Several steps of the entry process can serve as drug targets. Receptor antagonists prevent attachment of gp120 to the receptor or co-receptor and conformational changes within gp41 required for membrane fusion can be inhibited by fusion inhibitors. Enfuvirtide (T20, Fuzeon) is a peptide based on the gp41 sequence and is the only approved fusion inhibitor. It prevents membrane fusion by competitively binding to gp41 and blocking the formation of the post-fusion structure. New generations of T20-like peptides have been developed with improved potency and stability. Besides T20 and derivatives, other fusion inhibitors have been developed that target different domains of gp41. Here we discuss the development of fusion inhibitors, their mode of action and their potential for incorporation in future drug regimens.
Keywords: HIV, virus entry, antiviral peptide, fusion inhibitors, enfuvirtide, T20, VIRIP, resistance, HIV-1, envelope glycoprotein complex, human immunodeficiency virus type 1, gp41, gp120, Fuzeon, acquired immunodeficiency syndrome, Highly Active Antiretroviral Therapy (HAART), reverse transcriptase (RT), nucleoside analogue, non-nucleoside RT inhibitors, DNA strand elongation, zidovudine, stavudine, thymidine, didanosine, abacavir, guanine, viral Gag, Gag-Pol precursor, Saquinavir, ritonavir, indinavir, integrase, Maraviroc, BMS-378806, PRO542, immunoglobulin, vicriviroc, coronaviridae, TORO phase III study, HXB2 isolate, S138A, N126K, Cyclic depsipeptides, Siliquaria spongia mirabilis
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