Cysteine Cathepsin Inhibitors as Anti-Ebola Agents.
Cysteine Cathepsin Inhibitors as Anti-Ebola Agents.
复制标题
DOI：
10.1021/acsinfecdis.5b00130
复制
发表时间：
2016-03-11
影响因子：
5.3
通讯作者：
Bogyo M
中科院分区：
文献类型：
--
作者：
van der Linden WA;Schulze CJ;Herbert AS;Krause TB;Wirchnianski AA;Dye JM;Chandran K;Bogyo M
最近在西非爆发的埃博拉病毒突出了对靶向埃博拉病毒和其他丝状病毒的新型疗法的需求。丝状病毒需要由宿主细胞来源的半胱氨酸组织蛋白酶加工以进行生产性感染。在这里，我们报告的半胱氨酸组织蛋白酶抑制剂和随后的筛选，以确定化合物对病毒的进入和复制的有效活性的集中库的产生。我们的顶级化合物对半胱氨酸组织蛋白酶显示出高效和广谱的活性，并能够有效阻止埃博拉和马尔堡病毒的进入。这些药物是开发抗丝状病毒治疗剂的有希望的先导药物。
The recent Ebola virus outbreak in western Africa highlights the need for novel therapeutics that target Ebola virus and other filoviruses. Filoviruses require processing by host cell-derived cysteine cathepsins for productive infection. Here we report the generation of a focused library of cysteine cathepsin inhibitors and subsequent screening to identify compounds with potent activity against viral entry and replication. Our top compounds show highly potent and broad-spectrum activity against cysteine cathepsins and were able to effectively block entry of Ebola and Marburg viruses. These agents are promising leads for development as antifilovirus therapeutics.