Format

Send to

Choose Destination
J Med Virol. 2019 Feb 22. doi: 10.1002/jmv.25440. [Epub ahead of print]

Antimalarial drugs and their metabolites are potent Zika virus inhibitors.

Han Y1, Pham HT1,2, Xu H1, Quan Y1, Mesplède T1,2,3,4.

Author information

1
McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada.
2
Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
3
Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
4
Division of Infectious Diseases, Jewish General Hospital, Faculty of Medicine, McGill University, Montréal, Québec, Canada.

Abstract

Studies aimed at repurposing existing drugs revealed that some antimalarial compounds possess anti-Zika virus (anti-ZIKV) activity. Here, we further tested 14 additional antimalarial drugs and their metabolites or analogs for anti-ZIKV activity using a phenotypic screening approach. We identified four compounds with varying anti-ZIKV activity, including a metabolite of amodiaquine termed desethylamodiaquine (DAQ) and N-desethylchloroquine (DECQ), a metabolite of chloroquine, which both exhibited low micromolar effective concentrations against three different ZIKV strains. Two other compounds termed dihydroartemisinin (DHA) and quinidine (QD) exhibited only partial inhibition of ZIKV replication. Characterization of the inhibitory mechanisms of DAQ and DECQ showed that both drugs target the entry step as well as postentry events of the viral replication cycle. These hits represent attractive starting points for future optimization of new anti-ZIKV drug candidates derived from antimalarial drugs and their analogs.

KEYWORDS:

Zika; antimalarial; antiviral drug; phenotypic screening; repurposing

PMID:
30801742
DOI:
10.1002/jmv.25440

Supplemental Content

Loading ...
Support Center