Cysteine Cathepsin Inhibitors as Anti-Ebola Agents

van der Linden WA, Schulze CJ, Herbert AS, Krause TB, Wirchnianski AS, Dye JM, Chandran K and Bogyo M. 2016. ACS Infect Dis In press.

[doi: 10.1021/acsinfecdis.5b00130]  [Download PDF]


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 anti-filovirus therapeutics.