Suppression of hepatitis C virus replication by cyclin-dependent kinase inhibitors
Suppression of hepatitis C virus replication by cyclin-dependent kinase inhibitors
复制标题
细胞周期蛋白依赖性激酶抑制剂抑制丙型肝炎病毒复制
DOI：
10.1016/j.antiviral.2014.05.011
复制
发表时间：
2014
影响因子：
7.6
通讯作者：
Akio Nomoto
中科院分区：
文献类型：
--
作者：
Tsubasa Munakata;Makoto Inada;Yuko Tokunaga;Takaji Wakita;Michinori Kohara;Akio Nomoto
丙型肝炎病毒（HCV）是慢性肝炎的病原体。尽管HCV感染患者的标准治疗包括聚乙二醇干扰素加利巴韦林，但这种治疗与严重的副作用和高成本相关，并且在某些感染特定HCV基因型的患者中失败。为了解决这个问题，我们正在开发小分子细胞周期蛋白依赖性激酶（CDK）抑制剂作为新的抗HCV候选药物。先前的数据表明，HCV复制被视网膜母细胞瘤蛋白抑制，视网膜母细胞瘤蛋白本身通过CDK介导的磷酸化而失活。在这里，我们报道了CDK抑制剂在体外和体内抑制HCV复制，并且CDK4是HCV有效复制所必需的。这些发现为靶向宿主因子的新型抗HCV药物的开发提供了线索。
Hepatitis C virus (HCV) is a causative agent of chronic hepatitis. Although the standard therapy for HCV-infected patients consists of pegylated interferon plus ribavirin, this treatment is associated with serious side effects and high costs, and fails in some patients infected with specific HCV genotypes. To address this problem, we are developing small-molecule inhibitors of cyclin-dependent kinases (CDKs) as novel anti-HCV drug candidates. Previous data showed that HCV replication is inhibited by retinoblastoma protein, which is itself inactivated by CDK-mediated phosphorylation. Here, we report that CDK inhibitors suppress HCV replicationin vitroandin vivo, and that CDK4 is required for efficient HCV replication. These findings shed light on the development of novel anti-HCV drugs that target host factors.