A Plant-Derived Flavonoid Inhibits Entry of All HCV Genotypes Into Human Hepatocytes.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Keppler, Oliver T
MetadataShow full item record
AbstractBACKGROUND & AIMS: Interferon-based therapies for hepatitis C virus (HCV) infection are limited by side effects and incomplete response rates, particularly among transplant recipients. We screened a library of plant-derived small molecules to identify HCV inhibitors with novel mechanisms. METHODS: We isolated phenolic compounds from Marrubium peregrinum L (Lamiaceae). Replication of HCV RNA, virus production, and cell entry were monitored using replicons and infectious HCV. Inhibition of HCV was measured in hepatoma cells and primary human hepatocytes using luciferase reporter gene assays, core enzyme-linked immunosorbent assays, or infectivity titration. We tested the bioavailability of the compound in mice. RESULTS: We identified a flavonoid, ladanein (BJ486K), with unreported antiviral activity and established its oral bioavailability in mice. Natural and synthetic BJ486K inhibited a post-attachment entry step, but not RNA replication or assembly; its inhibitory concentration 50% was 2.5 μm. BJ486K was effective against all major HCV genotypes, including a variant that is resistant to an entry inhibitor; it prevented infection of primary human hepatocytes. Combined administration of BJ486K and cyclosporine A had a synergistic effect in inhibition of HCV infection. CONCLUSIONS: BJ486K has oral bioavailability and interferes with entry of HCV into cultured human hepatocytes. It synergizes with cyclosporine A to inhibit HCV infection. Its inhibitory effects are independent of HCV genotype, including a variant that is resistant to an entry inhibitor against scavenger receptor class B type I. Flavonoid derivatives therefore might be developed as components of combination therapies because they are potent, broadly active, inhibitors of HCV entry that could prevent graft reinfection after liver transplantation.
CitationA Plant-Derived Flavonoid Inhibits Entry of All HCV Genotypes Into Human Hepatocytes. 2012:notGastroenterology
AffiliationDivision of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
The following license files are associated with this item:
- Glucocorticosteroids increase cell entry by hepatitis C virus.
- Authors: Ciesek S, Steinmann E, Iken M, Ott M, Helfritz FA, Wappler I, Manns MP, Wedemeyer H, Pietschmann T
- Issue date: 2010 May
- Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry.
- Authors: Lin LT, Chung CY, Hsu WC, Chang SP, Hung TC, Shields J, Russell RS, Lin CC, Li CF, Yen MH, Tyrrell DL, Lin CC, Richardson CD
- Issue date: 2015 Mar
- (-)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry.
- Authors: Calland N, Albecka A, Belouzard S, Wychowski C, Duverlie G, Descamps V, Hober D, Dubuisson J, Rouillé Y, Séron K
- Issue date: 2012 Mar
- A novel small molecule inhibitor of hepatitis C virus entry.
- Authors: Baldick CJ, Wichroski MJ, Pendri A, Walsh AW, Fang J, Mazzucco CE, Pokornowski KA, Rose RE, Eggers BJ, Hsu M, Zhai W, Zhai G, Gerritz SW, Poss MA, Meanwell NA, Cockett MI, Tenney DJ
- Issue date: 2010 Sep 2
- Multiple effects of Honokiol on the life cycle of hepatitis C virus.
- Authors: Lan KH, Wang YW, Lee WP, Lan KL, Tseng SH, Hung LR, Yen SH, Lin HC, Lee SD
- Issue date: 2012 Jul