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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
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
SAFC
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
5-(N-Ethyl-N-isopropyl)amiloride
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Ammonium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
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Ammonium chloride, 99.998% trace metals basis
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Ammonium-14N chloride, 99.99 atom % 14N, 15N-depleted, 99% (CP)
Sigma-Aldrich
Ammonium chloride, 99.99% trace metals basis
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E-64d, protease inhibitor
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Simvastatin, ≥97% (HPLC), solid
Sigma-Aldrich
Atovaquone, ≥98% (HPLC)
Sigma-Aldrich
Efavirenz, ≥98% (HPLC)