An orally available, small-molecule interferon inhibits viral replication.
An orally available, small-molecule interferon inhibits viral replication.
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DOI：
10.1038/srep00259
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发表时间：
2012
影响因子：
4.6
通讯作者：
Sudoh, Masayuki
中科院分区：
文献类型：
--
作者：
Konishi, Hideyuki;Okamoto, Koichi;Ohmori, Yusuke;Yoshino, Hitoshi;Ohmori, Hiroshi;Ashihara, Motooki;Hirata, Yuichi;Ohta, Atsunori;Sakamoto, Hiroshi;Hada, Natsuko;Katsume, Asao;Kohara, Michinori;Morikawa, Kazumi;Tsukuda, Takuo;Shimma, Nobuo;Foster, Graham R.;Alazawi, William;Aoki, Yuko;Arisawa, Mikio;Sudoh, Masayuki
大多数急性丙型肝炎病毒（HCV）感染会变成慢性，有些会发展为肝硬化或肝细胞癌。标准治疗涉及基于干扰素（IFN）-α的方案，并且蛋白酶抑制剂的开发显著提高了治疗的疗效。然而，关于IFN的注射形式和副作用仍然存在一些问题。在这里，我们报告了一种口服，小分子I型IFN受体激动剂，直接转导IFN信号级联和刺激抗病毒基因的表达。与I型IFN一样，小分子化合物在小鼠体内和体外诱导IFN刺激基因（ISG）表达以获得抗病毒活性，ISG诱导机制归因于化合物与IFN-α受体2（细胞表面IFN信号传导的关键分子）之间的直接相互作用。我们的研究强调了口服活性干扰素样药物的重要性，无论是作为抗病毒感染的治疗方法还是作为潜在的干扰素替代品。
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.
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影响因子：
3.7
作者：
Farnsworth A;Flaman AS;Prasad SS;Gravel C;Williams A;Yauk CL;Li X
通讯作者：
Li X
影响因子：
64.8
作者：
Hemmi, H;Takeuchi, O;Akira, S
通讯作者：
Akira, S
影响因子：
158.5
作者：
Jacobson, Ira M.;McHutchison, John G.;Zeuzem, Stefan
通讯作者：
Zeuzem, Stefan
DOI：
10.1196/annals.1443.020
发表时间：
2008-01-01
期刊：
YEAR IN IMMUNOLOGY 2008
影响因子：
--
作者：
Kawai, Taro;Akira, Shizuo
通讯作者：
Akira, Shizuo
影响因子：
82.9
作者：
Mercer, DF;Schiller, DE;Kneteman, NM
通讯作者：
Kneteman, NM