Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein

Ting Chun Hung, Alagie Jassey, Ching Hsuan Liu, Chien Ju Lin, Chun Ching Lin, Shu Hui Wong, Jonathan Y. Wang, Ming Hong Yen, Liang Tzung Lin

Research output: Contribution to journalArticle

Abstract

Background: Despite the advent of direct-acting antivirals (DAAs), HCV remains an important public health problem globally. There is at present no effective vaccine against the virus, and the DAAs in current use cannot prevent de novo infection, including in liver transplant setting wherein donor livers inevitably become re-infected. Developing inhibitors to HCV entry using nature-derived small molecules may help to expand/complement the current treatment options. Purpose: In this study, we explored the effect of the plant alkaloid berberine (BBR) on HCV early viral entry. Methods: Cell culture-derived HCV (HCVcc), viral pseudoparticles bearing HCV glycoproteins (HCVpp), and entry-related assays were employed to assess BBR's bioactivity. Molecular docking was used to predict BBR-HCV glycoproteins interaction, and the compound's antiviral activity was confirmed against HCVcc infection of primary human hepatocytes (PHHs). Results: BBR specifically impeded HCVcc attachment and entry/fusion steps without inactivating the free virus particles or affecting the expression of host cell entry factors and post-entry viral replication. BBR also effectively inhibited infection by viral pseudoparticles expressing HCV E1/E2 glycoproteins and molecular docking analysis pointed at potential interaction with HCV E2. Finally, BBR could suppress HCVcc infection of PHHs. Conclusions: We identified BBR as a potent HCV entry inhibitor, which merits further evaluation particularly for use in transplant setting against graft re-infection by HCV.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalPhytomedicine
Volume53
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Berberine
Virus Internalization
Hepacivirus
Glycoproteins
Antiviral Agents
Infection
Transplants
Hepatocytes
Molecular Docking Simulation
Liver
Virus Diseases
Alkaloids
Virion
Vaccines
Public Health
Cell Culture Techniques
Viruses

Keywords

  • Alkaloid
  • Antiviral
  • Berberine
  • Entry inhibitor
  • HCV
  • Natural product

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

Cite this

Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein. / Hung, Ting Chun; Jassey, Alagie; Liu, Ching Hsuan; Lin, Chien Ju; Lin, Chun Ching; Wong, Shu Hui; Wang, Jonathan Y.; Yen, Ming Hong; Lin, Liang Tzung.

In: Phytomedicine, Vol. 53, 01.02.2019, p. 62-69.

Research output: Contribution to journalArticle

Hung, TC, Jassey, A, Liu, CH, Lin, CJ, Lin, CC, Wong, SH, Wang, JY, Yen, MH & Lin, LT 2019, 'Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein', Phytomedicine, vol. 53, pp. 62-69. https://doi.org/10.1016/j.phymed.2018.09.025
Hung, Ting Chun ; Jassey, Alagie ; Liu, Ching Hsuan ; Lin, Chien Ju ; Lin, Chun Ching ; Wong, Shu Hui ; Wang, Jonathan Y. ; Yen, Ming Hong ; Lin, Liang Tzung. / Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein. In: Phytomedicine. 2019 ; Vol. 53. pp. 62-69.
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AB - Background: Despite the advent of direct-acting antivirals (DAAs), HCV remains an important public health problem globally. There is at present no effective vaccine against the virus, and the DAAs in current use cannot prevent de novo infection, including in liver transplant setting wherein donor livers inevitably become re-infected. Developing inhibitors to HCV entry using nature-derived small molecules may help to expand/complement the current treatment options. Purpose: In this study, we explored the effect of the plant alkaloid berberine (BBR) on HCV early viral entry. Methods: Cell culture-derived HCV (HCVcc), viral pseudoparticles bearing HCV glycoproteins (HCVpp), and entry-related assays were employed to assess BBR's bioactivity. Molecular docking was used to predict BBR-HCV glycoproteins interaction, and the compound's antiviral activity was confirmed against HCVcc infection of primary human hepatocytes (PHHs). Results: BBR specifically impeded HCVcc attachment and entry/fusion steps without inactivating the free virus particles or affecting the expression of host cell entry factors and post-entry viral replication. BBR also effectively inhibited infection by viral pseudoparticles expressing HCV E1/E2 glycoproteins and molecular docking analysis pointed at potential interaction with HCV E2. Finally, BBR could suppress HCVcc infection of PHHs. Conclusions: We identified BBR as a potent HCV entry inhibitor, which merits further evaluation particularly for use in transplant setting against graft re-infection by HCV.

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