Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4894-4910
Number of pages17
JournalViruses
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 10 2015

Fingerprint

Magnolia
Lignans
Dengue Virus
Virus Diseases
Cricetinae
Arbovirus Infections
honokiol
Kidney
Replicon
Viral Genes
Dengue
Endosomes
Endocytosis
Virion
Antiviral Agents
Glycoproteins
Vaccines

Keywords

  • Antiviral
  • Dengue virus
  • Honokiol
  • Magnolia

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Fang, C. Y., Chen, S. J., Wu, H. N., Ping, Y. H., Lin, C. Y., Shiuan, D., ... Huang, K. J. (2015). Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection. Viruses, 7(9), 4894-4910. https://doi.org/10.3390/v7092852

Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection. / Fang, Chih Yeu; Chen, Siang Jyun; Wu, Huey Nan; Ping, Yueh Hsin; Lin, Ching Yen; Shiuan, David; Chen, Chi Long; Lee, Ying Ray; Huang, Kao Jean.

In: Viruses, Vol. 7, No. 9, 10.09.2015, p. 4894-4910.

Research output: Contribution to journalArticle

Fang, CY, Chen, SJ, Wu, HN, Ping, YH, Lin, CY, Shiuan, D, Chen, CL, Lee, YR & Huang, KJ 2015, 'Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection', Viruses, vol. 7, no. 9, pp. 4894-4910. https://doi.org/10.3390/v7092852
Fang, Chih Yeu ; Chen, Siang Jyun ; Wu, Huey Nan ; Ping, Yueh Hsin ; Lin, Ching Yen ; Shiuan, David ; Chen, Chi Long ; Lee, Ying Ray ; Huang, Kao Jean. / Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection. In: Viruses. 2015 ; Vol. 7, No. 9. pp. 4894-4910.
@article{477585f933d44c2e80af81f3c267e18a,
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.",
keywords = "Antiviral, Dengue virus, Honokiol, Magnolia",
author = "Fang, {Chih Yeu} and Chen, {Siang Jyun} and Wu, {Huey Nan} and Ping, {Yueh Hsin} and Lin, {Ching Yen} and David Shiuan and Chen, {Chi Long} and Lee, {Ying Ray} and Huang, {Kao Jean}",
year = "2015",
month = "9",
day = "10",
doi = "10.3390/v7092852",
language = "English",
volume = "7",
pages = "4894--4910",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Honokiol, a lignan biphenol derived from the Magnolia tree, inhibits dengue virus type 2 infection

AU - Fang, Chih Yeu

AU - Chen, Siang Jyun

AU - Wu, Huey Nan

AU - Ping, Yueh Hsin

AU - Lin, Ching Yen

AU - Shiuan, David

AU - Chen, Chi Long

AU - Lee, Ying Ray

AU - Huang, Kao Jean

PY - 2015/9/10

Y1 - 2015/9/10

N2 - 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.

AB - 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.

KW - Antiviral

KW - Dengue virus

KW - Honokiol

KW - Magnolia

UR - http://www.scopus.com/inward/record.url?scp=84941566213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941566213&partnerID=8YFLogxK

U2 - 10.3390/v7092852

DO - 10.3390/v7092852

M3 - Article

VL - 7

SP - 4894

EP - 4910

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 9

ER -