title: Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection.
abstract: Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co-localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection.
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. phildts@gmail.com.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,Taiwan. 610013122@ems.ndhu.edu.tw.
authors.forename: Siang-Jyun
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan. hnwu@gate.sinica.edu.tw.
authors.forename: Huey-Nan
authors.initials: HN
authors.lastname: Wu
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University,Taipei 112, Taiwan. yhping@ym.edu.tw.|Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan. yhping@ym.edu.tw.
authors.forename: Yueh-Hsin
authors.initials: YH
authors.lastname: Ping
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,Taiwan. jouyuan22@gmail.com.
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,Taiwan. shiuan@mail.ndhu.edu.tw.
authors.forename: David
authors.initials: D
authors.lastname: Shiuan
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan. chencl@tmu.edu.tw.|Department of Pathology, Taipei Medical University Hospital, Taipei Medical University,Taipei 110, Taiwan. chencl@tmu.edu.tw.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Chiayi Christian Hospital, Chiayi 600, Taiwan. yingray.lee@gmail.com.|Department of Nursing, Min-Hwei College of Health Care Management, Tainan 73658, Taiwan. yingray.lee@gmail.com.
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,Taiwan. kj-huang@dcb.org.tw.|Institute of Biologics, Development Center for Biotechnology, New Taipei City 22180, Taiwan. kj-huang@dcb.org.tw.
authors.forename: Kao-Jean
authors.initials: KJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D006224:Cricetinae; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000998:Antiviral Agents; D001713:Biphenyl Compounds; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Magnolia; antiviral; dengue virus; honokiol