Roger J Pomerantz; David L Horn


Nat Med. 2003;9(7) 

In This Article

2003: Fusion Inhibitors

Progress in drug development continues, as new classes of drugs are introduced. A very recent example is enfuvirtide (T-20), approved for use by the FDA on 13 March 2003.[65] Enfuvirtide and T-1249 are peptides of the extracellular domain of the transmembrane segment (gp41) of the HIV-1 envelope. When HIV-1 binds to host cell receptors, a conformational change occurs in gp41 which results in the 'springloaded' formation of coiled-coil helices in preparation of viral entry (Fig. 4). Enfuvirtide is a linear, 36-amino-acid synthetic peptide that inhibits HIV-1 entry into host cells by targeting the transient conformation of the fusion portion of the HIV-1 envelope glycoprotein in gp,[41] thereby preventing the full conformational changes required for the fusion of viral and cellular membranes.[67] Enfuvirtide, when combined with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in patients for whom other drug treatments have failed. This new drug has several limitations: it has to be delivered by sub-cutaneous injection, it is expensive and it is difficult to manufacture a relatively long chain peptide for human administration.[67] Other similar-acting peptides, including T-1249,[68] are now being tested in the clinic.