An orally available, small-molecule interferon inhibits viral replication
| Autor: | William Alazawi, Masayuki Sudoh, Michinori Kohara, Nobuo Shimma, Atsunori Ohta, Mikio Arisawa, Yuko Aoki, Asao Katsume, Natsuko Hada, Hitoshi Yoshino, Hiroshi Ohmori, Yuichi Hirata, Hiroshi Sakamoto, Kazumi Morikawa, Takuo Tsukuda, Motooki Ashihara, Yusuke Ohmori, Koichi Okamoto, Hideyuki Konishi, Graham R. Foster |
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| Rok vydání: | 2011 |
| Předmět: |
Agonist
medicine.drug_class Cell Blotting Western Administration Oral Hepacivirus Pharmacology Biology Real-Time Polymerase Chain Reaction Virus Replication Virus Article Mice Interferon In vivo medicine Animals Phosphorylation Receptor Multidisciplinary Surface Plasmon Resonance Virology In vitro medicine.anatomical_structure Viral replication Interferon Type I medicine.drug Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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