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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
Sertraline hydrochloride, ≥98% (HPLC)
Sigma-Aldrich
Teicoplanin
Sigma-Aldrich
Lomerizine dihydrochloride, ≥98% (HPLC), powder
Sigma-Aldrich
Ammonium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Supelco
Clomipramine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Ammonium chloride, 99.99% trace metals basis
Sigma-Aldrich
Ammonium chloride, 99.998% trace metals basis
Sigma-Aldrich
Paroxetine hydrochloride hemihydrate, ≥98% (HPLC), powder
Sigma-Aldrich
Sodium pyruvate, BioXtra, ≥99%
Sigma-Aldrich
cis-(Z)-Flupenthixol dihydrochloride, ≥98% (HPLC), solid
Sigma-Aldrich
Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
Sigma-Aldrich
Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
Sigma-Aldrich
Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
Sigma-Aldrich
Sodium pyruvate, ReagentPlus®, ≥99%
Sigma-Aldrich
Aripiprazole, ≥98% (HPLC)
Sigma-Aldrich
Mycophenolate mofetil, ≥98% (HPLC)
Sigma-Aldrich
Benztropine mesylate, ≥98% (HPLC)
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Simvastatin, ≥97% (HPLC), solid
Sigma-Aldrich
Atovaquone, ≥98% (HPLC)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
SAFC
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Ammonium-14N chloride, 99.99 atom % 14N, 15N-depleted, 99% (CP)
Sigma-Aldrich
Clomipramine hydrochloride, ≥98% (HPLC), powder
Sigma-Aldrich
E-64d, protease inhibitor