title: Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry.
abstract: A preventive vaccine against hepatitis C virus (HCV) infection remains unavailable and newly developed drugs against viral replication are complicated by potential drug-resistance and high cost. These issues justify the need to develop alternative antiviral agents and expand the scope of strategies for the treatment of hepatitis C, such as targeting viral entry. In this study, we explore the bioactivity of Limonium sinense (L. sinense) and its purified constituents against HCV life cycle using subgenomic replicon and infectious HCV culture systems. Data indicated that the water extract from the underground part of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non-cytotoxic concentrations. LS-UW targeted early HCV infection without affecting viral replication, translation, and cell-to-cell transmission, and blocked viral attachment and post-attachment entry/fusion steps. Bioactivity analysis of major constituents from LS-UW through viral infectivity/entry assays revealed that gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could suppress HCV infection of primary human hepatocytes. Due to their potency and ability to target HCV early viral entry, LS-UW and GA may be of value for further development as prospective antivirals against HCV.
authors: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Wen-Chan
authors: WC
authors: Hsu
authors: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Shun-Pang
authors: SP
authors: Chang
authors: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
authors: Lie-Chwen
authors: LC
authors: Lin
authors: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Chia-Lin
authors: CL
authors: Li
authors: Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada.
authors: Christopher D
authors: CD
authors: Richardson
authors: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: aalin@kmu.edu.tw.
authors: Chun-Ching
authors: CC
authors: Lin
authors: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: ltlin@tmu.edu.tw.
authors: Liang-Tzung
authors: LT
authors: Lin
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D005707:Gallic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D029606:Plumbaginaceae / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010936:Plant Extracts; D005707:Gallic Acid
keywords: Antivirals; Gallic acid; Hepatitis C virus; Limonium sinense; Natural products; Viral entry inhibition