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J Antimicrob Chemother. 2014 Aug;69(8):2123-31. doi: 10.1093/jac/dku091. Epub 2014 Apr 7.

The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry.

Author information

  • 1Institute for Molecular Biology, Hannover Medical School, Hannover, Germany Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • 2Institute for Molecular Biology, Hannover Medical School, Hannover, Germany.
  • 3Institute for Virology, University of Marburg, Marburg, Germany.
  • 4Infection Biology Unit, German Primate Center, Göttingen, Germany.
  • 5Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
  • 6Department of Nephrology, Hannover Medical School, Hannover, Germany.
  • 7Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • 8Institute for Molecular Biology, Hannover Medical School, Hannover, Germany Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany vonhahn.thomas@mh-hannover.de.

Abstract

OBJECTIVES:

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties.

METHODS:

We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds.

RESULTS:

We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant.

CONCLUSIONS:

The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry.

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

calcium channels; cationic amphiphiles; haemorrhagic fever

PMID:
24710028
[PubMed - indexed for MEDLINE]
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