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Multiple effects of honokiol on the life cycle of hepatitis C virus
Author(s) -
Lan KengHsin,
Wang YingWen,
Lee WeiPing,
Lan KengLi,
Tseng SzuHan,
Hung LiRong,
Yen SangHue,
Lin HanChieh,
Lee ShouDong
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02621.x
Subject(s) - honokiol , internal ribosome entry site , virology , replicon , ns5a , hepatitis c virus , biology , vesicular stomatitis virus , ns5b , viral replication , virus , hepacivirus , translation (biology) , pharmacology , gene , messenger rna , biochemistry , plasmid
Background Honokiol, a small active molecular compound extracted from magnolia, has recently been shown to inhibit hepatitis C virus ( HCV ) infection in vitro . Aims This study further characterized aspects of the HCV lifecycle affected by the antiviral functions of honokiol. Methods The influence of honokiol on HCV infection, entry, translation and replication was assessed in Huh‐7.5.1 cells using cell culture‐derived HCV ( HCV cc), HCV pseudo‐type ( HCV pp) and sub‐genomic replicons. Results Honokiol had strong antiviral effect against HCV cc infection at non‐toxic concentrations. Combined with interferon‐α, its inhibitory effect on HCV cc was more profound than that of ribavirin. Honokiol inhibited the cell entry of lentiviral particles pseudo‐typed with glycoproteins from HCV genotypes 1a, 1b, and 2a, but not of the vesicular stomatitis virus. It had inefficient activity on HCV internal ribosome entry site ( IRES )‐translation at concentrations with significant anti‐ HCV cc effects. The expression levels of components of replication complex, NS 3, NS 5A and NS 5B, were down‐regulated by honokiol in a dose‐dependent manner. It also inhibited HCV replication dose dependently in both genotypes 1b and 2a sub‐genomic replicons. Conclusions Honokiol inhibits HCV infection by targeting cell entry and replication and, only at a concentration >30 μM, IRES ‐mediated translation of HCV life cycle. Based on its high therapeutic index ( LD 50 / EC 90 = 5.4), honokiol may be a promising drug for the treatment of HCV infection.