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Title: Drug repurposing of quinine as antiviral against dengue virus infection
Authors: Shilu Malakar
Liji Sreelatha
Thanyaporn Dechtawewat
Sansanee Noisakran
Pa thai Yenchitsomanus
Justin Jang Hann Chu
Thawornchai Limjindaporn
Yong Loo Lin School of Medicine
Faculty of Medicine, Siriraj Hospital, Mahidol University
Thailand National Science and Technology Development Agency
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology;Medicine
Issue Date: 15-Aug-2018
Citation: Virus Research. Vol.255, (2018), 171-178
Abstract: © 2018 Elsevier B.V. Dengue virus (DENV) disease outbreaks continue to develop across the globe with significant associated mortality and economic burden, yet no treatment has been approved to combat this virus. In an attempt to identify novel drug candidates as therapeutics for DENV infection, we evaluated four US Food and Drug Administration (FDA) approved drugs including aminolevullic acid, azelaic acid, mitoxantrone hydrochloride, and quinine sulfate, and tested their ability to inhibit DENV replication using focus-forming unit assay to quantify virus production. Of the four investigated compounds, quinine was found to have the most pronounced anti-DENV activity. Quinine inhibited DENV production of DENV by about 80% compared to untreated controls, while the other three drugs decreased virus production by only about 50%. Moreover, quinine inhibited DENV production of all four serotypes of DENV. Reduction in virus production was documented in three different cell lines of human origin. Quinine significantly inhibited DENV replication by reducing DENV RNA and viral protein synthesis in a dose-dependent manner. In addition, quinine ameliorated expression of genes related to innate immune response. These findings suggest the efficacy of quinine for stimulating antiviral genes to reduce DENV replication. The antiviral activity of quinine observed in this study may have applicability in the development of new drug therapies against DENV.
ISSN: 18727492
Appears in Collections:Scopus 2018

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