ArticleJournal of hepatology2012
Understanding silibinin's modes of action against HCV using viral kinetic modeling.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials.BioMed research international · 2014Pooled it
- A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV.Antiviral therapy · 2015Trial
- Reply to: Modeling challenges of hepatitis D virus kinetics during bulevirtide-based therapy.JHEP reports : innovation in hepatology · 2025Article
- Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.Viruses · 2024Article
- A Comprehensive Review on the Antibacterial, Antifungal, Antiviral, and Antiparasitic Potential of Silybin.Antibiotics (Basel, Switzerland) · 2024Review
- Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review.Archives of microbiology · 2023Review
- Efficient Methods for Parameter Estimation of Ordinary and Partial Differential Equation Models of Viral Hepatitis Kinetics.Mathematics (Basel, Switzerland) · 2020Article
- Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin.Viruses · 2019Article
- Antiviral Activities of Silymarin and Derivatives.Molecules (Basel, Switzerland) · 2019Review
- A pharmacokinetic/viral kinetic model to evaluate treatment of chronic HCV infection with a non-nucleoside polymerase inhibitor.Antiviral therapy · 2018Article
- Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.Molecules (Basel, Switzerland) · 2017Review
- Modeling Viral Spread.Annual review of virology · 2016Review
- Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy.Journal of viral hepatitis · 2016Article
- Modeling Suggests a Mechanism of Synergy Between Hepatitis C Virus Entry Inhibitors and Drugs of Other Classes.CPT: pharmacometrics & systems pharmacology · 2015Article
- HCV Kinetic Models and Their Implications in Drug Development.CPT: pharmacometrics & systems pharmacology · 2015Review
- Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics.Liver international : official journal of the International Association for the Study of the Liver · 2015Article
- Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.Antiviral therapy · 2015Article
- Viral kinetic modeling: state of the art.Journal of pharmacokinetics and pharmacodynamics · 2014Review
- A hepatitis C virus infection model with time-varying drug effectiveness: solution and analysis.PLoS computational biology · 2014Article
- Small molecule inhibitors of HCV replication from pomegranate.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsLegalon® SIL (SIL) is a chemically hydrophilized version of silibinin that has exhibited high antiviral effectiveness against hepatitis C virus (HCV). Its main mode of action (MOA) remains unclear, with contradicting in vitro studies supporting either suppression of entry and cell-to-cell spread or suppression of viral RNA synthesis as the main MOA. We sought to provide new insights into SIL's MOA in HCV genotype-1/4 patients receiving intravenous SIL monotherapy for 7 days via mathematical modeling.
methodsChanges in HCV RNA in 25 patients receiving 10, 15, or 20mg/kg/day of SIL were analyzed and modeled using viral kinetic methods.
resultsIn 15 patients, the virus declined in a biphasic manner, in which a sharp drop between days 0 and 2 was followed by a slower second phase of decline. In 10 patients, the initial decline was weaker and the virus declined in a single phase over the 7-day period. The blocking production effectiveness, ε, was dose-dependent with mean ε=0.49 and 0.89 in the 10 or 15 and 20mg/kg/day dosing groups, respectively (p=0.02). The effectiveness of blocking viral infection, η, was estimated as 0.60 with no significant differences across dosing groups. For all patients, the mean rate of viral load decline measured between days 2 and 7 was high (0.3 log(10)IU/ml/day), i.e., 4-fold higher than typically observed during the 2nd phase of (pegylated)-interferon-α±ribavirin treatment.
conclusionsModeling HCV kinetics in vivo suggests that SIL may block both viral infection and viral production/release with its main dose-dependent effect being blocking viral production/release.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.