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首页> 外文期刊>Scientific reports. >Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide
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Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide

机译：化学阵列系统，识别新型乙型肝炎病毒进入抑制剂的平台靶向牛磺酸钠COT转化多肽

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Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture. One of such compound, NPD8716, a coumarin derivative, interacted with NTCP and inhibited HBV infection without causing cytotoxicity. Consistent with its NTCP interaction capacity, this compound was shown to block viral attachment to host hepatocytes. NPD8716 also prevented the infection with hepatitis D virus, but not hepatitis C virus, in agreement with NPD8716 specifically inhibiting NTCP-mediated infection. Analysis of derivative compounds showed that the anti-HBV activity of compounds was apparently correlated with the affinity to NTCP and the capacity to impair NTCP-mediated bile acid uptake. These results are the first to show that the chemical array technology represents a powerful platform to identify novel viral entry inhibitors.
机译：目前的抗乙型肝炎病毒（HBV）药剂包括干扰素和核苷酸（T）IDE类似物有效地抑制HBV感染。然而，由于难以从慢性感染的肝脏中消除HBV，迫切需要靶向靶向新分子的替代抗HBV药剂。在这项研究中，我们将化学阵列应用于与牛磺酸钠COTRANSPORTING多肽（NTCP）相互作用的小分子的高通量筛选，用于HBV的进入受体。从大约30,000种化合物中，我们确定了NTCP交互剂的74名候选者，并且显示出五个中的五种患者在细胞培养中抑制HBV感染。这种化合物，NPD8716，香豆素衍生物，与NTCP相互作用并抑制HBV感染而不引起细胞毒性。与其NTCP相互作用容量一致，显示该化合物以阻断病毒附着以宿主肝细胞。 NPD8716还预防乙型肝炎病毒感染，而不是丙型肝炎病毒，同意NPD8716特异性抑制NTCP介导的感染。衍生化合物的分析表明，化合物的抗HBV活性明显与NTCP的亲和力和损害NTCP介导的胆汁酸摄取的能力相关。这些结果是首先表明化学阵列技术代表了识别新型病毒进入抑制剂的强大平台。

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