Abstract

Without a vaccine, hepatitis C virus (HCV) remains a global medical and socio-economic burden, predisposing about 170 million carriers worldwide to end-stage liver diseases including cirrhosis and hepatocellular carcinoma. Although the recently developed direct-acting antivirals (DAAs) have revolutionized hepatitis C treatment, most of them are unsuitable for monotherapy due to risks of resistance, thus necessitating combination with interferon (IFN)-alpha, ribavirin, or additional DAAs. More importantly, the high cost associated with the DAAs restricts their accessibility to most parts of the world. Developing novel cost-effective anti-HCV therapeutics may help expand the scope of antivirals and treatment strategies against hepatitis C. Herein, we applied an activity-based and fraction-guided analysis of extracts from the medicinal plant Phyllanthus urinaria (P. urinaria), which yielded fraction 13 (F13) as possessing the most potent inhibitory activity against early viral entry of cell-culture HCV infection. Chemical analysis (silica gel chromatography followed by ESI LC-MS plus 1H and 13C NMR) of F13 identified loliolide (LOD), a monoterpenoid lactone, as a novel inhibitor of HCV entry. Specifically, LOD could efficiently inactivate HCV free virus particles, abrogate viral attachment, and impede viral entry/fusion, with minimal effect on viral replication/translation, particle production, and induction of type I IFN host antiviral immune response. ELISA-based binding analysis confirmed the monoterpenoid's ability in efficiently blocking HCV particle attachment to the host cell surface. Furthermore, LOD could inhibit infection by several genotypic strains of HCV. This is the first report characterizing P. urinaria and its bioactive compound LOD as potent HCV entry inhibitors, which merit further evaluation for development as candidate antiviral agents against hepatitis C.

Original languageEnglish
Pages (from-to)58-68
Number of pages11
JournalAntiviral Research
Volume130
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Phyllanthus
Virus Internalization
Hepacivirus
Antiviral Agents
Hepatitis C
Monoterpenes
Virion
Medical Economics
Virus Attachment
Costs and Cost Analysis
Interferon Type I
End Stage Liver Disease
loliolide
Ribavirin
Silica Gel
Lactones
Virus Diseases
Medicinal Plants
Interferon-alpha
Gel Chromatography

Keywords

  • Antiviral
  • Hepatitis C
  • Loliolide
  • Natural product
  • Phyllanthus urinaria
  • Viral entry

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Activity-based and fraction-guided analysis of Phyllanthus urinaria identifies loliolide as a potent inhibitor of hepatitis C virus entry. / Chung, Chueh Yao; Liu, Ching Hsuan; Burnouf, Thierry; Wang, Guey Horng; Chang, Shun Pang; Jassey, Alagie; Tai, Chen Jei; Tai, Cheng Jeng; Huang, Ching Jang; Richardson, Christopher D.; Yen, Ming Hong; Lin, Chun Ching; Lin, Liang Tzung.

In: Antiviral Research, Vol. 130, 01.06.2016, p. 58-68.

Research output: Contribution to journalArticle

Chung, Chueh Yao ; Liu, Ching Hsuan ; Burnouf, Thierry ; Wang, Guey Horng ; Chang, Shun Pang ; Jassey, Alagie ; Tai, Chen Jei ; Tai, Cheng Jeng ; Huang, Ching Jang ; Richardson, Christopher D. ; Yen, Ming Hong ; Lin, Chun Ching ; Lin, Liang Tzung. / Activity-based and fraction-guided analysis of Phyllanthus urinaria identifies loliolide as a potent inhibitor of hepatitis C virus entry. In: Antiviral Research. 2016 ; Vol. 130. pp. 58-68.
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