The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication

Hui-Chen Hung; Shin-Ru Shih; Teng-Yuan Chang; Ming-Yu Fang; John T-A Hsu

doi:10.1371/journal.pone.0111331

The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication

PLoS One. 2014 Nov 20;9(11):e111331. doi: 10.1371/journal.pone.0111331. eCollection 2014.

Authors

Hui-Chen Hung¹, Shin-Ru Shih², Teng-Yuan Chang¹, Ming-Yu Fang¹, John T-A Hsu³

Affiliations

¹ Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan.
² 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.
³ Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds / administration & dosage*
Aniline Compounds / pharmacology
Animals
Antiviral Agents / administration & dosage*
Antiviral Agents / pharmacology
Apoptosis / drug effects
Cell Line
Chlorocebus aethiops
Crotonates
Cytokines / genetics
Cytokines / metabolism
Drug Repositioning
Drug Synergism
Drug Therapy, Combination
Enterovirus A, Human / drug effects*
Enterovirus A, Human / physiology
Enterovirus Infections / drug therapy*
Enterovirus Infections / immunology
Humans
Hydroxybutyrates / administration & dosage*
Hydroxybutyrates / pharmacology
Lithium Chloride / administration & dosage*
Lithium Chloride / pharmacology
Nitriles
Toluidines
Vero Cells
Virus Replication / drug effects

Substances

Aniline Compounds
Antiviral Agents
Crotonates
Cytokines
Hydroxybutyrates
Nitriles
Toluidines
teriflunomide
Lithium Chloride

Grants and funding

This work was supported by the Ministry of Science and Technology (MOST) Grants MOST 101-2811-B-400-023 and BP-101-PP-01 to J.T.-A.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.