期刊
VIRUS RESEARCH
卷 255, 期 -, 页码 171-178出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2018.07.018
关键词
Dengue virus; Quinine sulfate; Replication; Innate immune response
类别
资金
- Siriraj Research and Development Fund, Faculty of Medicine Siriraj Hospital, Mahidol University [R016133006]
- Research Assistantship Scholarship from the Faculty of Graduate Studies, Mahidol University
- Thailand Research Fund [IRG 5980006]
- Singapore Ministry of Education [2017-T2-1-078]
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.
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