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Multiple effects of silymarin on the hepatitis C virus lifecycle
Author(s) -
Wagoner Jessica,
Negash Amina,
Kane Olivia J.,
Martinez Laura E.,
Nahmias Yaakov,
Bourne Nigel,
Owen David M.,
Grove Joe,
Brimacombe Claire,
McKeating Jane A.,
Pécheur EveIsabelle,
Graf Tyler N.,
Oberlies Nicholas H.,
Lohmann Volker,
Cao Feng,
Tavis John E.,
Polyak Stephen J.
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23587
Subject(s) - silybum marianum , woodchuck hepatitis virus , virology , biology , ns5b , hepatitis c virus , virus , silibinin , viral entry , hepatitis b virus , viral replication , pharmacology , hepadnaviridae , hepacivirus , botany
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. H EPATOLOGY 2010