title: Multifaceted action of Fuzeon as virus-cell membrane fusion inhibitor.
abstract: The viral peptide fusion inhibitor Fuzeon (T-20/DP178/enfuvirtide) is an essential part of the drug combination that has significantly increased the quality of life and life span of many acquired immuno-deficiency syndrome (AIDS) patients. Its development as a drug preceded the elucidation of its precise inhibitory mechanism, as well as its molecular targets. The initial model was that Fuzeon inhibits human immunodeficiency virus (HIV) entry by targeting one site within the viral transmembrane envelope protein. Herein, we describe the emerging discoveries that extend this model towards a multifaceted mechanism for the drug in targeting HIV. This significantly advances the understanding of how viruses enter host cells and opens a new window of opportunity for designing future viral fusion inhibitors.
authors.affiliation: The Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Ashkenazi
authors.forename: Yael
authors.initials: Y
authors.lastname: Wexler-Cohen
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
mesh_terms: D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008561:Membrane Fusion / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide