title: A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.
abstract: Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Johansen
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Lisa Evans
authors.initials: LE
authors.lastname: DeWald
authors.affiliation: University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Shoemaker
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hoffstrom
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Calli M
authors.initials: CM
authors.lastname: Lear-Rooney
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stossel
authors.affiliation: University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nelson
authors.affiliation: University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: Sue E
authors.initials: SE
authors.lastname: Delos
authors.affiliation: University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Simmons
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Grenier
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Pierce
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Pajouhesh
authors.affiliation: Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA. Bioinformatics Program, Boston University, 20 Cummington Street, Boston, MA 02215, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lehár
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Glass
authors.affiliation: University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
authors.forename: Judith M
authors.initials: JM
authors.lastname: White
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA. gene.olinger@nih.gov.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D015764:Bepridil / Q000494:pharmacology; D017277:Drug Approval; D029043:Ebolavirus / Q000187:drug effects; D019142:Hemorrhagic Fever, Ebola / Q000628:therapy*; D006801:Humans; D051379:Mice; D015335:Molecular Probes; D020280:Sertraline / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D015335:Molecular Probes; D015764:Bepridil; D020280:Sertraline