title: Inhibition of dengue virus production and cytokine/chemokine expression by ribavirin and compound A.
abstract: Dengue virus (DENV) infection is a worldwide public health problem with an increasing magnitude. The severity of disease in the patients with DENV infection correlates with high viral load and massive cytokine production - the condition referred to as "cytokine storm". Thus, concurrent inhibition of DENV and cytokine production should be more effective for treatment of DENV infection. In this study, we investigated the effects of the antiviral agent - ribavirin (RV), and the anti-inflammatory compound - compound A (CpdA), individually or in combination, on DENV production and cytokine/chemokine transcription in human lung epithelial carcinoma (A549) cells infected with DENV. Initially, the cells infected with DENV serotype 2 (DENV2) was studied. The results showed that treatment of DENV-infected cells with RV could significantly reduce both DENV production and cytokine (IL-6 and TNF-α) and chemokine (IP-10 and RANTES) transcription while treatment of DENV-infected cells with CpdA could significantly reduce cytokine (IL-6 and TNF-α) and chemokine (RANTES) transcription. Combined RV and CpdA treatment of the infected cells showed greater reduction of DENV production and cytokine/chemokine transcription. Similar results of this combined treatment were observed for infection with any one of the four DENV (DENV1, 2, 3, and 4) serotypes. These results indicate that combination of the antiviral agent and the anti-inflammatory compound offers a greater efficiency in reduction of DENV and cytokine/chemokine production, providing a new therapeutic approach for DENV infection.
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Thidarath
authors.initials: T
authors.lastname: Rattanaburee
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Mutita
authors.initials: M
authors.lastname: Junking
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Graduate Program in Biochemistry, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Aussara
authors.initials: A
authors.lastname: Panya
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Nunghathai
authors.initials: N
authors.lastname: Sawasdee
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Pucharee
authors.initials: P
authors.lastname: Songprakhon
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Aroonroong
authors.initials: A
authors.lastname: Suttitheptumrong
authors.affiliation: Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Thawornchai
authors.initials: T
authors.lastname: Limjindaporn
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: pathai.yen@mahidol.ac.th.
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003715:Dengue / Q000188:drug therapy / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D012254:Ribavirin / Q000494:pharmacology*; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D018925:Chemokines; D016207:Cytokines; D012254:Ribavirin; D014439:Tyramine
keywords: Chemokine; Compound A; Cytokine; Dengue virus; Ribavirin