title: The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication.
abstract: Enterovirus 71 (EV-A71) is a neurotropic virus that can cause severe complications involving the central nervous system. No effective antiviral therapeutics are available for treating EV-A71 infection and drug discovery efforts are rarely focused to target this disease. Thus, the main goal of this study was to discover existing drugs with novel indications that may effectively inhibit EV-A71 replication and the inflammatory cytokines elevation. In this study, we showed that LiCl, a GSK3β inhibitor, effectively suppressed EV-A71 replication, apoptosis and inflammatory cytokines production (Interleukin 6, Interleukin-1β) in infected cells. Furthermore, LiCl and an immunomodular agent were shown to strongly synergize with each other in suppressing EV-A71 replication. The results highlighted potential new treatment regimens in suppressing sequelae caused by EV-A71 replication.
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Medical Biotechnology & Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan; Clinical Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Teng-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Fang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: John T-A
authors.initials: JT
authors.lastname: Hsu
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D003437:Crotonates; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D058492:Drug Repositioning; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000502:physiology; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006885:Hydroxybutyrates / Q000008:administration & dosage* / Q000494:pharmacology; D018021:Lithium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D009570:Nitriles; D014052:Toluidines; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D000998:Antiviral Agents; D003437:Crotonates; D016207:Cytokines; D006885:Hydroxybutyrates; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D018021:Lithium Chloride