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

Lisa Evans Dewald; Julie Dyall; Jennifer M. Sword; Lisa Torzewski; Huanying Zhou; Elena Postnikova; Erin Kollins; Isis Alexander; Robin Gross; Yu Cong; Dawn M. Gerhardt; Reed F. Johnson; Gene G. Olinger; Michael R. Holbrook; Lisa E. Hensley; Peter B. Jahrling

doi:10.1093/infdis/jiy332

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

Lisa Evans Dewald
, Julie Dyall
, Jennifer M. Sword
, Lisa Torzewski
, Huanying Zhou
, Elena Postnikova
, Erin Kollins
, Isis Alexander
, Robin Gross
, Yu Cong
, Dawn M. Gerhardt
, Reed F. Johnson
, Gene G. Olinger
, Michael R. Holbrook
, Lisa E. Hensley
, Peter B. Jahrling

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

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 bepridils broad-spectrum anti-filovirus activity warranting further investigation of bepridil, or improved compounds with a similar mechanism, as a pan-filovirus therapeutic agent.

Original language	English (US)
Pages (from-to)	S588-S591
Journal	Journal of Infectious Diseases
Volume	218
DOIs	https://doi.org/10.1093/infdis/jiy332
State	Published - Nov 22 2018
Externally published	Yes

Keywords

antiviral
bepridil
Marburg virus.

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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10.1093/infdis/jiy332

Cite this

Dewald, L. E., Dyall, J., Sword, J. M., Torzewski, L., Zhou, H., Postnikova, E., Kollins, E., Alexander, I., Gross, R., Cong, Y., Gerhardt, D. M., Johnson, R. F., Olinger, G. G., Holbrook, M. R., Hensley, L. E., & Jahrling, P. B. (2018). The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease. Journal of Infectious Diseases, 218, S588-S591. https://doi.org/10.1093/infdis/jiy332

Dewald, LE, Dyall, J, Sword, JM, Torzewski, L, Zhou, H, Postnikova, E, Kollins, E, Alexander, I, Gross, R, Cong, Y, Gerhardt, DM, Johnson, RF, Olinger, GG, Holbrook, MR, Hensley, LE & Jahrling, PB 2018, 'The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease', Journal of Infectious Diseases, vol. 218, pp. S588-S591. https://doi.org/10.1093/infdis/jiy332

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title = "The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease",

abstract = "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 bepridils broad-spectrum anti-filovirus activity warranting further investigation of bepridil, or improved compounds with a similar mechanism, as a pan-filovirus therapeutic agent.",

keywords = "antiviral, bepridil, Marburg virus.",

author = "Dewald, \{Lisa Evans\} and Julie Dyall and Sword, \{Jennifer M.\} and Lisa Torzewski and Huanying Zhou and Elena Postnikova and Erin Kollins and Isis Alexander and Robin Gross and Yu Cong and Gerhardt, \{Dawn M.\} and Johnson, \{Reed F.\} and Olinger, \{Gene G.\} and Holbrook, \{Michael R.\} and Hensley, \{Lisa E.\} and Jahrling, \{Peter B.\}",

note = "Publisher Copyright: {\textcopyright} 2018. This article contains public sector information licensed under the Open Government Licence v3.0.",

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doi = "10.1093/infdis/jiy332",

language = "English (US)",

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AU - Dewald, Lisa Evans

AU - Dyall, Julie

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AU - Torzewski, Lisa

AU - Zhou, Huanying

AU - Postnikova, Elena

AU - Kollins, Erin

AU - Alexander, Isis

AU - Gross, Robin

AU - Cong, Yu

AU - Gerhardt, Dawn M.

AU - Johnson, Reed F.

AU - Olinger, Gene G.

AU - Holbrook, Michael R.

AU - Hensley, Lisa E.

AU - Jahrling, Peter B.

PY - 2018/11/22

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N2 - 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 bepridils broad-spectrum anti-filovirus activity warranting further investigation of bepridil, or improved compounds with a similar mechanism, as a pan-filovirus therapeutic agent.

AB - 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 bepridils broad-spectrum anti-filovirus activity warranting further investigation of bepridil, or improved compounds with a similar mechanism, as a pan-filovirus therapeutic agent.

KW - antiviral

KW - bepridil

KW - Marburg virus.

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SN - 0022-1899

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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