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Antiviral Res. 2017 Nov;147:19-28. doi: 10.1016/j.antiviral.2017.09.006. Epub 2017 Sep 18.

Pentagalloylglucose, a highly bioavailable polyphenolic compound present in Cortex moutan, efficiently blocks hepatitis C virus entry.

Author information

1
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany; Clinic for Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany; German Centre for Infection Research, Hannover-Braunschweig Site, Germany.
2
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
3
Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland; Federal Department of Home Affairs, Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland.
4
Department Clinical Chemistry, Microbiology and Immunology, Center for Vaccinology, Ghent University, Ghent, Belgium.
5
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
6
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada.
7
Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany; German Centre for Infection Research, Hannover-Braunschweig Site, Germany.
8
Clinic for Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
9
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany; German Centre for Infection Research, Hannover-Braunschweig Site, Germany. Electronic address: Thomas.pietschmann@twincore.de.

Abstract

Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection. We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV. One of the ZBDHW components, Penta-O-Galloyl-Glucose (PGG), was further analyzed for its mode of action in vitro, its antiviral activity in primary human hepatocytes as well as for its bioavailability and hepatotoxicity in mice. ZBDHW, its component Cortex Moutan and the compound PGG efficiently block entry of HCV of all major genotypes and also of the related flavivirus Zika virus. PGG does not disrupt HCV virion integrity and acts primarily during virus attachment. PGG shows an additive effect when combined with the well characterized HCV inhibitor Daclatasvir. Analysis of bioavailability in mice revealed plasma levels above tissue culture IC50 after a single intraperitoneal injection. In conclusion, PGG is a pangenotypic HCV entry inhibitor with high bioavailability. The low cost and wide availability of this compound make it a promising candidate for HCV combination therapies, and also emerging human pathogenic flaviviruses like ZIKV.

KEYWORDS:

Antivirals; Bioavailability; Cortex moutan; Entry inhibitor; Hepatitis C virus; Natural compounds; Penta-O-Galloyl-Glucose

PMID:
28923507
DOI:
10.1016/j.antiviral.2017.09.006
[Indexed for MEDLINE]

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