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Multiple effects of silymarin on the hepatitis C virus lifecycle

Wagoner, Jessica and Negash, Amina and Kane, Olivia J and Martinez, Laura E and Nahmias, Yaakov and Bourne, Nigel and Owen, David M and Grove, Joe and Brimacombe, Claire L and McKeating, Jane A and Pécheur, Eve-Isabelle and Graf, Tyler N and Oberlies, Nicholas H and Lohmann, Volker and Cao, Feng and Tavis, John E and Polyak, Stephen J (2010) Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology (Baltimore, Md.), 51 (6). pp. 1912-21. ISSN 1527-3350

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Identification Number/DOI: 10.1002/hep.23587

Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell.

Type of Work:Article
Date:2010 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:the American Association for the Study of Liver Diseases
ID Code:460
Refereed:YES
Local Holdings:
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