title: Synthesized peptide inhibitors of HIV-1 gp41-dependent membrane fusion.
abstract: Fusion of viral and cellular membranes is an essential step for HIV-1 infection. This process offers an attractive target for developing antiviral agents. T20 (Enfuvirtide, Fuzeon), a 36-amino acid peptide derived from the C-terminal heptad repeat region of HIV-1 gp41, is the first and only clinically approved HIV-1 fusion inhibitor that being used for treatment of HIV/AIDS patients failed to respond to current antiretroviral drugs. However, T20-resistance can be acquired rather easily in vitro and in vivo. T1249 is considered as a representative of the second generation fusion inhibitors, but its clinical evaluation was halted due to the problem of drug formulation. To overcome these challenges, a number of strategies have been applied to develop the third or next-generation inhibitors with the significantly improved antiviral activity and pharmacokinetic profiles. Promisingly, several peptides are currently under clinical trials, such as Sifuvirtide and VIR-576. Recently, several high resolution crystal structures of HIV-1 fusion inhibitor peptides were reported, which reveal the key residues or motifs underlying their potency against diverse HIV-1 variants. This review highlights the development of the representative peptide inhibitors of HIV-1 fusion toward providing some insights into the future of this class of anti-HIV drugs.
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China. yhe@ipb.pumc.edu.cn
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors*; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008561:Membrane Fusion / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1