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

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 t...

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Main Authors: Chih-Yeu Fang, Siang-Jyun Chen, Huey-Nan Wu, Yueh-Hsin Ping, Ching-Yen Lin, David Shiuan, Chi-Long Chen, Ying-Ray Lee, Kao-Jean Huang
Format: Article
Language:English
Published: MDPI AG 2015-09-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/7/9/2852
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author Chih-Yeu Fang
Siang-Jyun Chen
Huey-Nan Wu
Yueh-Hsin Ping
Ching-Yen Lin
David Shiuan
Chi-Long Chen
Ying-Ray Lee
Kao-Jean Huang
author_facet Chih-Yeu Fang
Siang-Jyun Chen
Huey-Nan Wu
Yueh-Hsin Ping
Ching-Yen Lin
David Shiuan
Chi-Long Chen
Ying-Ray Lee
Kao-Jean Huang
author_sort Chih-Yeu Fang
collection DOAJ
description 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.
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spelling doaj.art-93cb0630463a4645972c7e96bcb625932022-12-22T01:55:08ZengMDPI AGViruses1999-49152015-09-01794894491010.3390/v7092852v7092852Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 InfectionChih-Yeu Fang0Siang-Jyun Chen1Huey-Nan Wu2Yueh-Hsin Ping3Ching-Yen Lin4David Shiuan5Chi-Long Chen6Ying-Ray Lee7Kao-Jean Huang8Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, TaiwanDepartment of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 11529, TaiwanDepartment and Institute of Pharmacology, School of Medicine, National Yang-Ming University,Taipei 112, TaiwanDepartment of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,TaiwanDepartment of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,TaiwanDepartment of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, TaiwanDepartment of Medical Research, Chiayi Christian Hospital, Chiayi 600, TaiwanDepartment of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974,TaiwanDengue 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.http://www.mdpi.com/1999-4915/7/9/2852antiviralhonokioldengue virusMagnolia
spellingShingle Chih-Yeu Fang
Siang-Jyun Chen
Huey-Nan Wu
Yueh-Hsin Ping
Ching-Yen Lin
David Shiuan
Chi-Long Chen
Ying-Ray Lee
Kao-Jean Huang
Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
Viruses
antiviral
honokiol
dengue virus
Magnolia
title Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
title_full Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
title_fullStr Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
title_full_unstemmed Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
title_short Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
title_sort honokiol a lignan biphenol derived from the magnolia tree inhibits dengue virus type 2 infection
topic antiviral
honokiol
dengue virus
Magnolia
url http://www.mdpi.com/1999-4915/7/9/2852
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