Peptide entry inhibitors of enveloped viruses: the importance of interfacial hydrophobicity.
Peptide entry inhibitors of enveloped viruses: the importance of interfacial hydrophobicity.
复制标题
包膜病毒的肽进入抑制剂：界面疏水性的重要性。
DOI：
10.1016/j.bbamem.2014.04.015
复制
发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Wimley WC
中科院分区：
文献类型：
--
作者：
Badani H;Garry RF;Wimley WC
已知有许多多肽可以抑制被包裹的病毒进入细胞，其中一种多肽正成功地作为药物用于临床。本文就这类多肽的发现、抗病毒活性及其作用机制进行了综述。虽然已经通过各种方法(基于结构的、意外的、有意的、理性的和蛮力的)发现了多肽进入抑制剂，但我们在这里表明它们有一个共同的物理化学性质：它们至少具有一定程度的疏水性和/或两亲性，并且有与膜界面相互作用的倾向。我们认为，这种倾向驱动了许多肽进入抑制剂的共同作用机制，涉及与病毒和细胞膜的直接相互作用，以及与复杂的疏水蛋白质/脂类界面的相互作用，这些界面在病毒-细胞融合期间至少是瞬时暴露的。通过同时与膜界面和其他关键疏水表面相互作用，我们假设肽进入抑制剂可以通过改变膜的物理化学来发挥作用，融合蛋白界面连接膜，并通过这样做干扰细胞膜和病毒膜的融合。基于这一想法，我们提出了一种专注于假定的进入抑制剂的界面疏水性的方法，可以有效地发现新型的、广谱的病毒进入抑制剂。这篇文章是题为：界面活性多肽和蛋白质特刊的一部分。客座编辑：威廉·C·温利和卡琳娜·赫里斯托娃。包膜病毒融合和进入是未得到充分利用的治疗靶点。许多多肽能抑制包膜病毒进入细胞。许多多肽进入抑制剂有与膜界面相互作用的倾向。许多多肽进入抑制剂对多种无关病毒具有活性。提出的模型强调了界面疏水性在进入抑制中的作用。
There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In this review, we discuss the discovery, antiviral activity and mechanism of action of such peptides. While peptide entry inhibitors have been discovered by a wide variety of approaches (structure-based, accidental, intentional, rational and brute force) we show here that they share a common physical chemical property: they are at least somewhat hydrophobic and/or amphipathic and have a propensity to interact with membrane interfaces. We propose that this propensity drives a shared mechanism of action for many peptide entry inhibitors, involving direct interactions with viral and cellular membranes, as well as interactions with the complex hydrophobic protein/lipid interfaces that are exposed, at least transiently, during virus–cell fusion. By interacting simultaneously with the membrane interfaces and other critical hydrophobic surfaces, we hypothesize that peptide entry inhibitors can act by changing the physical chemistry of the membranes, and the fusion protein interfaces bridging them, and by doing so interfere with the fusion of cellular and viral membranes. Based on this idea, we propose that an approach that focuses on the interfacial hydrophobicity of putative entry inhibitors could lead to the efficient discovery of novel, broad-spectrum viral entry inhibitors. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Enveloped virus fusion and entry are underutilized therapeutic targets. Many peptides inhibit enveloped virus entry into cells. Many peptide entry inhibitors have a propensity to interact with membrane interfaces. Many peptide entry inhibitors are active against multiple, unrelated viruses. A proposed model emphasizes the role interfacial hydrophobicity on entry inhibition.
登录
查看更多内容
影响因子：
6.8
作者：
Backovic, Marija;Jardetzky, Theodore S.
通讯作者：
Jardetzky, Theodore S.
影响因子：
64.5
作者：
CARR, CM;KIM, PS
通讯作者：
KIM, PS
影响因子：
5.4
作者：
Basu, Arnab;Antanasijevic, Aleksandar;Bowlin, Terry L.
通讯作者：
Bowlin, Terry L.
影响因子：
5.4
作者：
Bai, Fengwei;Town, Terrence;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
5.4
作者：
Boyle, KA;Compton, T
通讯作者：
Compton, T