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

[11]

Nakazato Y, 2009, J ARRYTHM, V25, P4

[12]

PERELMAN MS, 1987, BRIT HEART J, V58, P339

[13] Target Identification and Mode of Action of Four Chemically Divergent Drugs against Ebolavirus Infection [J].

Ren, Jingshan ;

Zhao, Yuguang ;

Fry, Elizabeth E. ;

Stuart, David I. .

JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (03) :724-733

[14] Variation in the glycoprotein and VP35 genes of Marburg virus strains [J].

Sanchez, A ;

Trappier, SG ;

Stroher, U ;

Nichol, ST ;

Bowen, MD ;

Feldmann, H .

VIROLOGY, 1998, 240 (01) :138-146

[15] Toremifene interacts with and destabilizes the Ebola virus glycoprotein [J].

Zhao, Yuguang ;

Ren, Jingshan ;

Harlos, Karl ;

Jones, Daniel M. ;

Zeltina, Antra ;

Bowden, Thomas A. ;

Padilla-Parra, Sergi ;

Fry, Elizabeth E. ;

Stuart, David I. .

NATURE, 2016, 535 (7610) :169-+

← 1 2 →