Received: 21 August 2017
Accepted: 24 December 2017
The antimalarial drug amodiaquine possesses anti-ZIKA virus
Mark A. Wainberg
McGill University AIDS Centre, Lady Davis
Institute for Medical Research, Jewish General
Hospital, Montreal, Quebec, Canada
Faculty of Medicine, Department of
Microbiology and Immunology, McGill
University, Montreal, Quebec, Canada
Yingshan Han, PhD, on behalf of Mark A.
Wainberg, McGill University AIDS Centre,
Lady Davis Institute for Medical Research,
Jewish General Hospital, Montreal, Quebec,
Canadian Institutes of Health Research
Zika virus (ZIKV) outbreak has emerged as a global health threat, particularly in tropical
areas, over the past few years. No antiviral therapy or vaccine is available at present.
For these reasons, repurposing clinically approved drugs against ZIKV infection may
provide rapid and cost-effective global health benefits. Here, we explored this strategy
and screened eight FDA-approved drugs for antiviral activity against ZIKV using a cell-
based assay. Our results show that the antimalarial drug amodiaquine has anti-ZIKV
activity with EC
at low micromolar concentrations in cell culture. We further
characterized amodiaquine antiviral activity against ZIKV and found that it targets early
events of the viral replication cycle. Altogether, our results suggest that amodiaquine
may be efficacious for the treatment of ZIKV infection.
amodiaquine, antiviral drug, repurposing, Zika
Zika virus (ZIKV), belonging to the family of Flaviviridae, was first
isolated from a monkey in Uganda in 1947. Since then, ZIKV has
caused sporadic febrile illness with mild symptoms similar to that of
dengue virus (DENV). Recent outbreaks of disease caused by ZIKV
were reported in Brazil in May 2015, and the virus has now spread to
68 countries and territories as of December 2016, mostly in tropical
and subtropical regions across the Caribbean, Latin America, and Asia.
ZIKV is a mosquito-borne virus that causes symptoms such as mild
fever, skin rashes, headache, and joint pains. Additionally, recent
studies have shown conclusive links between ZIKV and two serious
conditions: microcephaly in newborns and neurological disorders such
as Guillain-Barré syndrome in adults.
Currently there is no antiviral or
vaccine available. Because of the threat to public health worldwide,
the World Health Organization (WHO) declared a global emergency in
February 2016. Thus, there is an urgent need to discover and develop
effective anti-ZIKV drugs and vaccines as soon as possible.
To rapidly identify anti-ZIKV drugs to fight the current outbreak,
the repurposing of currently existing drugs with potential anti-ZIKV
activity may be practical. Such approved drugs already have well
documented safety and pharmacokinetic profiles, and might be able to
pass through regulatory pathways and be approved for clinical
evaluation more rapidly than new compounds.
developed cell-based antiviral assays for the screening of compounds
against human immunodeficiency virus (HIV) and DENV.
present study, we have established a cell-based assay in Vero cells for
the detection of ZIKV through the quantification of cytopathic effect
Abbreviations: AQ, amodiaquine; CC, cell control; CCID, cell culture infective dose; CCZ,
chlorcyclizine; CPE, cytopathic effect; CQ, chloroquine; DENV, dengue virus; DMEM,
Dulbecco's minimal essential medium; DMSO, dimethyl sulfoxide;; EBOV, Ebola virus; FBS,
fetal bovine serum; HIV, human immunodeficiency virus; MOI, multiplicity of infection;
MPA, mycophenolic acid; MTS, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-
2-(4-sulfophenyl)-2H-tetrazolium; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-
lium bromide; PBS, phosphate-buffered saline; PCZ, prochlorperazine dimaleate salt; PFU,
plaque forming units; PI, postinfection; QDH, quinacrine dihydrochloride; SD, standard
deviation; SI, selection index; TOA, time-of-addition; VC, virus control; ZIKV, Zika virus.
Institute at which work was performed: McGill University AIDS Centre, Lady Davis Institute
for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
© 2018 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/jmv J Med Virol. 2018;90:796–802.