title: Drug repurposing of minocycline against dengue virus infection.
abstract: Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon α (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection.
authors.affiliation: Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Shilpa Lekshmi
authors.initials: SL
authors.lastname: Leela
authors.affiliation: Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Chatchawan
authors.initials: C
authors.lastname: Srisawat
authors.affiliation: Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Gopinathan Pillai
authors.initials: GP
authors.lastname: Sreekanth
authors.affiliation: Medical Biotechnology Unit, National Cancer Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Thailand; Division of Dengue Hemorrhagic Fever Research, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sansanee
authors.initials: S
authors.lastname: Noisakran
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.affiliation: Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: thawornchai.lim@mahidol.ac.th.
authors.forename: Thawornchai
authors.initials: T
authors.lastname: Limjindaporn
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D003715:Dengue / Q000188:drug therapy* / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D058492:Drug Repositioning / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D008911:Minocycline / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D008911:Minocycline
keywords: Antiviral activity; Dengue virus infection; ERK1/2; Minocycline