title: Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs.
abstract: In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report here the identification of 53 drugs with activity of blocking Ebola VLP entry into cells. These 53 active compounds can be divided into categories including microtubule inhibitors, estrogen receptor modulators, antihistamines, antipsychotics, pump/channel antagonists, and anticancer/antibiotics. Several of these compounds, including microtubule inhibitors and estrogen receptor modulators, had previously been reported to be active in BSL-4 infectious Ebola virus replication assays and in animal model studies. Our assay represents a robust, effective and rapid high-throughput screen for the identification of lead compounds in drug development for the treatment of Ebola virus infection.
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kouznetsova
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA ; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA.
authors.forename: Carles
authors.initials: C
authors.lastname: Martínez-Romero
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Tawa
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Shinn
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Catherine Z
authors.initials: CZ
authors.lastname: Chen
authors.affiliation: Princess Margaret Cancer Centre, University Health Network , Toronto, ON M5T2M9 , Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Schimmer
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Sanderson
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: McKew
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA ; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA ; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
keywords: Antipsychotics; Ebola virus; Ebola virus glycoprotein; VP40; drug repurposing screen; estrogen receptor modulator; microtubule inhibitor; virus entry