Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.
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.
Department of Molecular Medicine, University of Padova, Padova 35121, Italy Department of Microbiology, The Public Health Agency of Sweden, Solna 171 82, Sweden.
Cristiano
C
Salata
Clinica Medica 1, Department of Medicine, University of Padova, Padova 35128, Italy.
Aldo
A
Baritussio
Department of Molecular Medicine, University of Padova, Padova 35121, Italy.
Denis
D
Munegato
Department of Molecular Medicine, University of Padova, Padova 35121, Italy.
Arianna
A
Calistri
Cardiovascular Therapy Research Laboratory, Clinical Research Center, University Hospital, Zurich 8091, Switzerland.
Huy Riem
HR
Ha
Department of Chemistry, University of Zurich, Zurich 8057, Switzerland.
Laurent
L
Bigler
Clinica Medica 1, Department of Medicine, University of Padova, Padova 35128, Italy.
Fabrizio
F
Fabris
Department of Molecular Medicine, University of Padova, Padova 35121, Italy.
Cristina
C
Parolin
Department of Molecular Medicine, University of Padova, Padova 35121, Italy giorgio.palu@unipd.it.
Giorgio
G
Palù
Department of Microbiology, The Public Health Agency of Sweden, Solna 171 82, Sweden Department for Laboratory Medicine, Karolinska Institute, Huddinge/Stockholm 141 83, Sweden National Veterinary Institute, Uppsala 751 89, Sweden.
Ali
A
Mirazimi
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D029043:Ebolavirus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D053586:Virus Internalization / Q000187:drug effects*
D000998:Antiviral Agents; D015104:3,4-Methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine; D000638:Amiodarone
amiodarone; cationic amphiphiles; dronedarone; ebola; filovirus; haemorrhagic fever