Header

UZH-Logo

Maintenance Infos

Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process


Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palu, Giorgio; Mirazimi, Ali (2015). Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process. FEMS Pathogens and Disease, 73(5):ftv032-ftv032.

Abstract

Ebola 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.

Abstract

Ebola 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.

Statistics

Citations

Dimensions.ai Metrics
16 citations in Web of Science®
15 citations in Scopus®
13 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 26 Jan 2016
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:May 2015
Deposited On:26 Jan 2016 11:37
Last Modified:27 Aug 2018 14:47
Publisher:Oxford University Press
ISSN:2049-632X
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/femspd/ftv032

Download

Download PDF  'Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 1MB
View at publisher