title: Tyrosine kinase/phosphatase inhibitors decrease dengue virus production in HepG2 cells.
abstract: Dengue virus is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. High rates of dengue virus replication and virion production are related to disease severity. To identify anti-DENV compounds, we performed cell-based ELISA testing to detect the level of DENV E protein expression. Among a total of 83 inhibitors, eight were identified as inhibitors with antiviral activity. Epidermal growth factor receptor inhibitor II (EGFR/ErbB-2/ErbB-4 inhibitor II) and protein tyrosine phosphatase inhibitor IV (PTP inhibitor IV) significantly inhibited dengue virus production and demonstrated low toxicity in hepatocyte cell lines. Our results suggest the efficacy of tyrosine kinase/phosphatase inhibitors in decreasing dengue virus production in HepG2 cells.
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
authors.affiliation: Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Jutatip
authors.initials: J
authors.lastname: Panaampon
authors.affiliation: Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Shilu
authors.initials: S
authors.lastname: Malakar
authors.affiliation: Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 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
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D056945:Hep G2 Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012367:RNA, Viral / Q000096:biosynthesis; D066247:Receptor, ErbB-4 / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins; C512478:EGFR protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4; D017027:Protein Tyrosine Phosphatases
keywords: Antiviral activity; Dengue virus; Epidermal growth factor receptor inhibitor; HepG2 cells; Protein tyrosine phosphatase inhibitor