Plos Pathog:研究发现药物阻断丙肝病毒复制的作用机制

2017-06-09 秋海 来宝网

在全球范围内,有7100万丙肝感染患者。经过数十年的感染后,慢性丙肝会进一步损坏肝脏,提高其发展成为肝病终期及肝癌的风险。如今,在美国,该病毒成为导致肝病死亡的主要原因。

在全球范围内,有7100万丙肝感染患者。经过数十年的感染后,慢性丙肝会进一步损坏肝脏,提高其发展成为肝病终期及肝癌的风险。如今,在美国,该病毒成为导致肝病死亡的主要原因

自研究开发了联合疗法后,丙肝对抗病毒药物具有了抵抗性,极有可能会导致治疗失败。在一组药物疗法中,抵抗性尤其重要,但其阻止病毒繁殖的作用机制知之不多。北卡罗来纳大学教堂山分校的研究人员首次发现知名NS5A抑制因子的抗病毒药物是如何与病毒作用的,并且他们的研究结果发现了丙肝病毒之间具有差异性。该研究结果已发表于PLOS Pathogens。

“当丙肝病毒感染肝细胞时,它在细胞内建立了复制复合物(RCs),”McGivern博士说,他是UNC传染病分所的副教授以及本研究的主要作者。“这些可看作是一个工厂,专门复制病毒的遗传物质。我们想知道,利用NS5A抑制剂治疗后,被感染的细胞内这些工厂还会存在多久。”

在这之前,该研究团队已发现NS5A抑制剂可阻断新的RCs的形成,但并不会影响到已经存在的RCs,但其会在治疗过程中最终消失。该团队使用NS5A抑制剂测试了已经存在的RCs 的半衰率,最后发现不同的丙肝病菌就会具有不同的停止阶段。

大部分的患者使用抗病毒治疗后可将他们的丙肝感染清除干净,”McGivern。“但是,大概有5%的患者在治疗过程中失败,这通常是因为药物的抵抗性。我们的研究发现对这一小部分患者具有非常重要的意义。治疗失败是否是因为复制复合物的转化较慢?某些丙肝菌株是否需要更长时间的治疗才起作用?深入探究这些问题将有助于更有效地治疗更多的病毒。”

原始出处

Tiffany Benzine, Ryan Brandt, William C. Lovell, et al. NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains, PLOS Pathogens (2017). DOI: 10.1371/journal.ppat.1006343.

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    2017-06-09 天涯183

    非常好的文章,学习了,很受益

    0

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