Cysteine Cathepsin Inhibitors as Anti-Ebola Agents
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- 作者：Wouter A. van der Linden ; Christopher J. Schulze ; Andrew S. Herbert ; Tyler B. Krause ; Ariel A. Wirchnianski ; John M. Dye ; Kartik Chandran ; Matthew Bogyo
- 刊名：ACS Infectious Diseases
- 出版年：2016
- 出版时间：March 11, 2016
- 年：2016
- 卷：2
- 期：3
- 页码：173-179
- 全文大小：449K
- ISSN：2373-8227
文摘
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.