The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein.
The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein.
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DOI：
10.1016/j.virol.2011.03.026
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发表时间：
2011-05-25
期刊：
影响因子：
3.7
通讯作者：
Glenn JS
中科院分区：
文献类型：
--
作者：
Lee C;Ma H;Hang JQ;Leveque V;Sklan EH;Elazar M;Klumpp K;Glenn JS
丙型肝炎病毒（HCV）非结构（NS）5A蛋白在通过膜相关复制复合物（RC）复制病毒RNA中起重要作用。最近，一种推定的NS 5A抑制剂BMS-790052在体外抑制HCV复制方面具有任何已知抗HCV化合物中最高的效力，并且在HCV感染患者中显示出有希望的临床效果。然而，这类新的潜在抗HCV治疗剂的确切作用机制仍不清楚。为了进一步了解其作用模式，我们试图检验BMS-790052的抗病毒作用可能通过干扰HCV RC的功能组装来介导的假设。我们观察到BMS-790052确实改变了NS 5A的亚细胞定位和生化分级。总之，我们的数据表明，NS 5A抑制剂如BMS-790052可以通过改变NS 5A在功能性RC中的适当定位来抑制病毒基因组复制。
The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, has the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.
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