Multifaceted action of Fuzeon as virus–cell membrane fusion inhibitor

• Published in: Biochimica et biophysica acta Vol. 1808; no. 10; pp. 2352 - 2358
• Main Authors: Ashkenazi, Avraham, Wexler-Cohen, Yael, Shai, Yechiel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2011
• Subjects: HIV entry inhibitor; HIV Envelope Protein gp41 - pharmacology; HIV Fusion Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - physiology; Membrane fusion; Membrane Fusion - drug effects; Peptide Fragments - pharmacology; Transmembrane protein; Viral envelope protein; Transmembrane protein; Membrane fusion; Viral envelope protein; HIV entry inhibitor
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2011.06.020

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. ► Fuzeon advances the understanding of how viral transmembrane envelope proteins facilitate membrane fusion. ► Fuzeon targets the cell membrane and multiple sites on gp41 and gp120. ► HIV fusion inhibitors are important candidates in AIDS therapy.