Ashkenazi Avraham, Wexler-Cohen Yael, Shai Yechiel
The Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Biochim Biophys Acta. 2011 Oct;1808(10):2352-8. doi: 10.1016/j.bbamem.2011.06.020. Epub 2011 Jul 5.
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.
病毒肽融合抑制剂福泽昂（T-20/DP178/恩夫韦肽）是一种药物组合的重要组成部分，该药物组合显著提高了许多获得性免疫缺陷综合征（艾滋病）患者的生活质量和寿命。它作为一种药物的研发先于其精确抑制机制及其分子靶点的阐明。最初的模型是福泽昂通过靶向病毒跨膜包膜蛋白内的一个位点来抑制人类免疫缺陷病毒（HIV）的进入。在此，我们描述了一些新发现，这些发现将该模型扩展为该药物靶向HIV的多方面机制。这显著推进了对病毒如何进入宿主细胞的理解，并为设计未来的病毒融合抑制剂打开了一扇新的机会之窗。
