Science Translational Medicine 2015-06-03

A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

Lisa M Johansen, Lisa Evans DeWald, Charles J Shoemaker, Benjamin G Hoffstrom, Calli M Lear-Rooney, Andrea Stossel, Elizabeth Nelson, Sue E Delos, James A Simmons, Jill M Grenier, Laura T Pierce, Hassan Pajouhesh, Joseph Lehár, Lisa E Hensley, Pamela J Glass, Judith M White, Gene G Olinger

Index: Sci. Transl. Med. 7 , 290ra89, (2015)

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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. Copyright © 2015, American Association for the Advancement of Science.