The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease

被引：20

作者：

DeWald, Lisa Evans ^{[1
,3
]}

Dyall, Julie ^{[1
]}

Sword, Jennifer M. ^{[1
]}

Torzewski, Lisa ^{[1
]}

Zhou, Huanying ^{[1
]}

Postnikova, Elena ^{[1
]}

Kollins, Erin ^{[1
]}

Alexander, Isis ^{[1
]}

Gross, Robin ^{[1
]}

Cong, Yu ^{[1
]}

Gerhardt, Dawn M. ^{[1
]}

Johnson, Reed F. ^{[2
]}

Olinger, Gene G., Jr. ^{[1
,4
]}

Holbrook, Michael R. ^{[1
]}

Hensley, Lisa E. ^{[1
]}

Jahrling, Peter B. ^{[1
,2
]}

机构：

[1] NIAID, Integrated Res Facil, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA

[2] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD USA

[3] Emergent BioSolut Inc, Gaithersburg, MD USA

[4] MRIGlobal Global Hlth Surveillance & Diagnost, Gaithersburg, MD USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2018年 / 218卷

关键词：

antiviral; bepridil; Marburg virus; GLYCOPROTEIN; AMIODARONE; TARGET; EBOLA;

D O I：

10.1093/infdis/jiy332

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

No therapeutics are approved for the treatment of filovirus infections. Bepridil, a calcium channel blocker developed for treating angina, was identified as a potent inhibitor of filoviruses in vitro, including Ebola and Marburg viruses, and Ebola virus in vivo. We evaluated the efficacy of bepridil in a lethal mouse model of Marburg virus disease. A dose of 12 mg/kg bepridil once or twice daily resulted in 80% or 90% survival, respectively. These data confirm bepridil's broad-spectrum anti-filovirus activity warranting further investigation of bepridil, or improved compounds with a similar mechanism, as a pan-filovirus therapeutic agent.

引用

页码：S588 / S591

页数：4

共 15 条

[1]

[Anonymous], 2011, NATL RES COUNCIL US, V8th, DOI [10.17226/12910, DOI 10.17226/12910]

[2] Discovering Drugs for the Treatment of Ebola Virus [J].

Sandra L. Bixler ;

Allen J. Duplantier ;

Sina Bavari .

Current Treatment Options in Infectious Diseases, 2017, 9 (3) :299-317

[3] Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists [J].

Cheng, Han ;

Lear-Rooney, Calli M. ;

Johansen, Lisa ;

Varhegyi, Elizabeth ;

Chen, Zheng W. ;

Olinger, Gene G. ;

Rong, Lijun .

JOURNAL OF VIROLOGY, 2015, 89 (19) :9932-9938

[4] Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus [J].

Cong, Yu ;

Dyall, Julie ;

Hart, Brit J. ;

DeWald, Lisa Evans ;

Johnson, Joshua C. ;

Postnikova, Elena ;

Zhou, Huanying ;

Gross, Robin ;

Rojas, Oscar ;

Alexander, Isis ;

Josleyn, Nicole ;

Zhang, Tengfei ;

Michelotti, Julia ;

Janosko, Krisztina ;

Glass, Pamela J. ;

Flint, Mike ;

McMullan, Laura K. ;

Spiropoulou, Christina F. ;

Mierzwa, Tim ;

Guha, Rajarshi ;

Shinn, Paul ;

Michael, Sam ;

Klumpp-Thomas, Carleen ;

McKnight, Crystal ;

Thomas, Craig ;

Eakin, Ann E. ;

O'Loughlin, Kathleen G. ;

Green, Carol E. ;

Catz, Paul ;

Mirsalis, Jon C. ;

Honko, Anna N. ;

Olinger, Gene G., Jr. ;

Bennett, Richard S. ;

Holbrook, Michael R. ;

Hensley, Lisa E. ;

Jahrling, Peter B. .

PLOS ONE, 2016, 11 (11)

[5] BEPRIDIL - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC USE IN STABLE ANGINA-PECTORIS [J].

HOLLINGSHEAD, LM ;

FAULDS, D ;

FITTON, A .

DRUGS, 1992, 44 (05) :835-857

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

Johansen, Lisa M. ;

DeWald, Lisa Evans ;

Shoemaker, Charles J. ;

Hoffstrom, Benjamin G. ;

Lear-Rooney, Calli M. ;

Stossel, Andrea ;

Nelson, Elizabeth ;

Delos, Sue E. ;

Simmons, James A. ;

Grenier, Jill M. ;

Pierce, Laura T. ;

Pajouhesh, Hassan ;

Lehar, Joseph ;

Hensley, Lisa E. ;

Glass, Pamela J. ;

White, Judith M. ;

Olinger, Gene G. .

SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (290)

[7] FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection [J].

Johansen, Lisa M. ;

Brannan, Jennifer M. ;

Delos, Sue E. ;

Shoemaker, Charles J. ;

Stossel, Andrea ;

Lear, Calli ;

Hoffstrom, Benjamin G. ;

DeWald, Lisa Evans ;

Schornberg, Kathryn L. ;

Scully, Corinne ;

Lehar, Joseph ;

Hensley, Lisa E. ;

White, Judith M. ;

Olinger, Gene G. .

SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (190)

[8] Characterization of Marburg virus glycoprotein in viral entry [J].

Manicassamy, Balaji ;

Wang, Jizhen ;

Rumschlag, Emily ;

Tymen, Stephanie ;

Volchkova, Valentina ;

Volchkov, Viktor ;

Rong, Lijun .

VIROLOGY, 2007, 358 (01) :79-88

[9] Bepridil and Amiodarone Simultaneously Target the Alzheimer's Disease β- and γ-Secretase via Distinct Mechanisms [J].

Mitterreiter, Stefan ;

Page, Richard M. ;

Kamp, Frits ;

Hopson, Jessika ;

Winkler, Edith ;

Ha, Huy-Riem ;

Hamid, Runa ;

Herms, Jochen ;

Mayer, Thomas U. ;

Nelson, Deborah J. ;

Steiner, Harald ;

Stahl, Tobias ;

Zeitschel, Ulrike ;

Rossner, Steffen ;

Haass, Christian ;

Lichtenthaler, Stefan F. .

JOURNAL OF NEUROSCIENCE, 2010, 30 (26) :8974-8983

[10] Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease [J].

Morgan, Anthony J. ;

Platt, Frances M. ;

Lloyd-Evans, Emyr ;

Galione, Antony .

BIOCHEMICAL JOURNAL, 2011, 439 :349-374

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