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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

Supelco
Sertraline hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Dimethyl sulfoxide, Vetec, reagent grade, 99%
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Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
Sigma-Aldrich
Sodium pyruvate, SAJ special grade, ≥95.0%
Sigma-Aldrich
Sertraline hydrochloride, ≥98% (HPLC)
Sigma-Aldrich
Lomerizine dihydrochloride, ≥98% (HPLC), powder
Supelco
Clomipramine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Teicoplanin
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Aripiprazole, ≥98% (HPLC)
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Mycophenolate mofetil, ≥98% (HPLC)
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Benztropine mesylate, ≥98% (HPLC)
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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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Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
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Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
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Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
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Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
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Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
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Dimethyl sulfoxide, PCR Reagent
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Dimethyl sulfoxide, for molecular biology
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Paroxetine hydrochloride hemihydrate, ≥98% (HPLC), powder
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Dimethyl sulfoxide, anhydrous, ≥99.9%
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cis-(Z)-Flupenthixol dihydrochloride, ≥98% (HPLC), solid
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Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%