Multiple effects of silymarin on the hepatitis C virus lifecycle.
Multiple effects of silymarin on the hepatitis C virus lifecycle.
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DOI：
10.1002/hep.23587
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发表时间：
2010-06
期刊：
影响因子：
13.5
通讯作者：
Polyak, Stephen J.
中科院分区：
文献类型：
--
作者：
Wagoner, Jessica;Negash, Amina;Kane, Olivia J.;Martinez, Laura E.;Nahmias, Yaakov;Bourne, Nigel;Owen, David M.;Grove, Joe;Brimacombe, Claire;McKeating, Jane A.;Pecheur, Eve-Isabelle;Graf, Tyler N.;Oberlies, Nicholas H.;Lohmann, Volker;Cao, Feng;Tavis, John E.;Polyak, Stephen J.
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit HCV infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against 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 JFH-1 genotype 2a NS5B-dependent RNA polymerase activity at concentrations 5–10 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 5 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. While 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.
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