Multiple Effects of Silymarin on the Hepatitis C Virus Lifecycle

• DOI: 10.1002/hep.23587
• Publication Date: 2010-03-29T20:17:30Z
• Authors: Jessica Wagoner; Amina Negash; Olivia J. Kane; Laura E. Martinez; Yaakov Nahmias; Nigel Bourne; David M. Owen; Joe Grove; Claire Brimacombe; Jane A. McKeating; Eve-Isabelle Pécheur; Tyler N. Graf; Nicholas H. Oberlies; Volker Lohmann; Feng Cao; John E. Tavis; Stephen J. Polyak
• Keywords: 0301 basic medicine; QR Microbiology; Hepacivirus; R Medicine (General); Viral Nonstructural Proteins; Virus Internalization; Antiviral Agents; 3. Good health; 03 medical and health sciences; Cell Line, Tumor; Humans; QR180 Immunology; QR355 Virology; Silymarin

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. Hepatology 2010