title: Cysteine Cathepsin Inhibitors as Anti-Ebola Agents.
abstract: 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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, United States.
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van der Linden
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schulze
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, United States.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Herbert
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
authors.forename: Tyler B
authors.initials: TB
authors.lastname: Krause
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, United States.
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Wirchnianski
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Dye
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
authors.forename: Kartik
authors.initials: K
authors.lastname: Chandran
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
keywords: Ebola virus; cathepsin inhibitor; filovirus; inhibition of host cell entry