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Viruses 2015, 7(9), 4894-4910;

Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection

Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,Taiwan
Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University,Taipei 112, Taiwan
Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan
Department of Pathology, Taipei Medical University Hospital, Taipei Medical University,Taipei 110, Taiwan
Department of Medical Research, Chiayi Christian Hospital, Chiayi 600, Taiwan
Department of Nursing, Min-Hwei College of Health Care Management, Tainan 73658, Taiwan
Institute of Biologics, Development Center for Biotechnology, New Taipei City 22180, Taiwan
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 6 May 2015 / Revised: 20 August 2015 / Accepted: 26 August 2015 / Published: 10 September 2015
(This article belongs to the Section Antivirals & Vaccines)
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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. View Full-Text
Keywords: antiviral; honokiol; dengue virus; Magnolia antiviral; honokiol; dengue virus; Magnolia

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Fang, C.-Y.; Chen, S.-J.; Wu, H.-N.; Ping, Y.-H.; Lin, C.-Y.; Shiuan, D.; Chen, C.-L.; Lee, Y.-R.; Huang, K.-J. Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection. Viruses 2015, 7, 4894-4910.

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