2. Academic Validation
  3. Drug repurposing of quinine as antiviral against dengue virus infection

Drug repurposing of quinine as antiviral against dengue virus infection

  • Virus Res. 2018 Aug 15;255:171-178. doi: 10.1016/j.virusres.2018.07.018.
Shilu Malakar 1,  Liji Sreelatha 2,  Thanyaporn Dechtawewat 3,  Sansanee Noisakran 4,  Pa-Thai Yenchitsomanus 3,  Justin Jang Hann Chu 5,  Thawornchai Limjindaporn 6
Affiliations

Affiliations

  • 1 Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Center of Research Excellence for Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 2 Siriraj Center of Research Excellence for Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Graduate Program in Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 3 Siriraj Center of Research Excellence for Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 4 Medical Biotechnology Unit, National Cancer Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
  • 5 Laboratory of Molecular RNA Virology and Antiviral Strategies, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
  • 6 Siriraj Center of Research Excellence for Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: [email protected].
PMID: 30055216 DOI: 10.1016/j.virusres.2018.07.018
Abstract

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.

Keywords

Dengue virus; Innate immune response; Quinine sulfate; Replication.

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