• Cristiano Salata, Aldo Baritussio, Denis Munegato, Arianna Calistri, Huy Riem Ha, Laurent Bigler, Fabrizio Fabris, Cristina Parolin, Giorgio Palù, and Ali Mirazimi.
• Department of Molecular Medicine, University of Padova, Padova 35121, Italy Department of Microbiology, The Public Health Agency of Sweden, Solna 171 82, Sweden.
• Pathog Dis. 2015 Jul 1; 73 (5).

AbstractEbola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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