Document Detail


An orally available, small-molecule interferon inhibits viral replication.
MedLine Citation:
PMID:  22355771     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most acute hepatitis C virus (HCV) infections become chronic and some progress to liver cirrhosis or hepatocellular carcinoma. Standard therapy involves an interferon (IFN)-α-based regimen, and efficacy of therapy has been significantly improved by the development of protease inhibitors. However, several issues remain concerning the injectable form and the side effects of IFN. Here, we report an orally available, small-molecule type I IFN receptor agonist that directly transduces the IFN signal cascade and stimulates antiviral gene expression. Like type I IFN, the small-molecule compound induces IFN-stimulated gene (ISG) expression for antiviral activity in vitro and in vivo in mice, and the ISG induction mechanism is attributed to a direct interaction between the compound and IFN-α receptor 2, a key molecule of IFN-signaling on the cell surface. Our study highlights the importance of an orally active IFN-like agent, both as a therapy for antiviral infections and as a potential IFN substitute.
Authors:
Hideyuki Konishi; Koichi Okamoto; Yusuke Ohmori; Hitoshi Yoshino; Hiroshi Ohmori; Motooki Ashihara; Yuichi Hirata; Atsunori Ohta; Hiroshi Sakamoto; Natsuko Hada; Asao Katsume; Michinori Kohara; Kazumi Morikawa; Takuo Tsukuda; Nobuo Shimma; Graham R Foster; William Alazawi; Yuko Aoki; Mikio Arisawa; Masayuki Sudoh
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-10
Journal Detail:
Title:  Scientific reports     Volume:  2     ISSN:  2045-2322     ISO Abbreviation:  Sci Rep     Publication Date:  2012  
Date Detail:
Created Date:  2012-02-22     Completed Date:  2013-04-12     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101563288     Medline TA:  Sci Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  259     Citation Subset:  IM    
Affiliation:
Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., Kamakura, Kanagawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Blotting, Western
Hepacivirus / drug effects*,  physiology
Interferon Type I / administration & dosage,  pharmacology*
Mice
Phosphorylation
Real-Time Polymerase Chain Reaction
Signal Transduction
Surface Plasmon Resonance
Virus Replication / drug effects*
Chemical
Reg. No./Substance:
0/Interferon Type I
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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