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

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

Science translational medicine (2015-06-05)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
cis-(Z)-Flupenthixol dihydrochloride, ≥98% (HPLC), solid
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Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
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Sodium pyruvate, ReagentPlus®, ≥99%
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Sodium pyruvate, BioXtra, ≥99%
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Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
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Ammonium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
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Paroxetine hydrochloride hemihydrate, ≥98% (HPLC), powder
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Ammonium chloride, 99.998% trace metals basis
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Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
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Mycophenolate mofetil, ≥98% (HPLC)
Supelco
Clomipramine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
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Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
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Sertraline hydrochloride, ≥98% (HPLC)
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Lomerizine dihydrochloride, ≥98% (HPLC), powder
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Teicoplanin
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Ammonium chloride, 99.99% trace metals basis
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Aripiprazole, ≥98% (HPLC)
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Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
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Benztropine mesylate, ≥98% (HPLC)
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E-64d, protease inhibitor
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Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
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Maprotiline hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
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Clemastine fumarate salt, ≥98% (HPLC)
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Sertraline hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
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Efavirenz, ≥98% (HPLC)
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Dimethyl sulfoxide, Vetec, reagent grade, 99%
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L-Glutamine
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Atovaquone, ≥98% (HPLC)
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Clomipramine hydrochloride, ≥98% (HPLC), powder
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Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture