eLife:科学家使用“病毒破解”分子,攻克乙肝病毒

2018-02-07 佚名 medicalxpress

印第安纳大学的研究人员在设计对抗乙肝病毒的药物方面取得了重要进展,乙肝病毒可导致肝脏衰竭和肝癌。

印第安纳大学的研究人员在设计对抗乙肝病毒的药物方面取得了重要进展,乙肝病毒可导致肝脏衰竭和肝癌。

据估计,全世界有20亿人在一生中感染了乙型肝炎病毒,其中约2.5亿人患有慢性感染,其中包括200万美国人。虽然有疫苗,但没有治愈方法。

这项研究发表在1月29日的《eLife》杂志上,它解释了乙肝病毒的结构在与实验药物结合时的变化。这种新型抗病毒药物的成员正在进行临床试验。

“我们的发现表明,这种药物可以在多个前沿攻击乙肝病毒,既防止复制,又杀死病毒的新副本,”亚当·兹洛特尼克(Adam Zlotnick)说。“如果我们聪明的话,我们可以利用这种药物同时发挥作用的多种方式。”

一种病毒通过劫持宿主的细胞机制来繁殖更多的病毒。大多数病毒都保护他们的基因物质DNA或RNA——在一种叫做“衣壳”的蛋白质外壳内。

在过去的20年里,Zlotnick的实验室通过研究病毒的物理特性,研究了病毒如何形成,从而阻止病毒感染。

Zlotnick说:“这种反应有点像把一副扑克牌扔到空中去建造泰姬陵——这是一种看起来很复杂的结构。”他的研究帮助发现了一种被称为核心蛋白质变构调制器(CpAMs)的分子,它破坏衣壳蛋白组装。

CpAM分子通过使它们的壳不正确的组装来攻击病毒,从而阻断病毒的生命周期。以前,CpAMs被认为只能够在衣壳形成过程中破坏病毒,之后它的DNA被保护在坚硬的外壳内。

这项新的研究发现,即使是在已经组装好的外壳上,分子也能分解。

为了让他们的发现,IU科学家们将CpAM与一种叫做tamraa的化学物质结合在一起,这种化学物质在一些红色的唇膏中使用,使其更加荧光,在实验中更容易被发现。使用低温电子显微镜,他们发现小的CpAM分子可以使大的,足球形状的病毒衣壳弯曲和扭曲。

Zlotnick说:“最大的影响是病毒衣壳不像以前认为的那样难以穿透。”另一个可能更重要的含义是,如果这种类型的干扰作用于乙肝病毒,它也可能对其他病毒起作用。

“大约有一半的已知病毒家族有像足球一样的衣壳;例子包括小儿麻痹症和疱疹。“这项研究可能会导致更好的治疗方法,因为衣壳破裂后的机制可能导致药物对其中任何一种产生不利影响。”

尽管在这项研究中使用的分子并不是临床试验的分子之一,Zlotnick说这个机制揭示了实验药物的行为。接下来,Zlotnick希望在临床试验中对CpAMs进行类似的研究。

原始出处:

Christopher John Schlicksup, Joseph Che-Yen Wang, Samson Francis, et.al. Hepatitis B virus core protein allosteric modulators can distort and disrupt intact capsids. elife  Jan 29, 2018

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    2018-09-28 clmlylxy
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    2018-06-22 膀胱癌
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    2018-02-08 神功盖世

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    2018-02-08 jihuaijun1112

    学习学习学习

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    2018-02-07 1e17414fm02(暂无匿称)

    学习

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许多疾病在医学是上不可能或者是很难完全治愈的,乙型肝炎就是这样一种疾病。因此,医学上就出现了一个词——临床治愈(Clinical cure)。但是,现在乙肝治愈有了新含义,是同之前的“临床治愈”完全不一样的新概念。

Sci Trans Med:乙肝新药进入临床阶段,有望彻底治愈乙肝

德州生物医学研究所西南国家灵长类动物研究中心(SNPRC)的研究人员们开始了慢性乙型肝炎病毒(HBV)新药的临床试验。测试结果显示,这种新颖的治疗方法和药物传递机制是安全有效的,研究结果发表在《国际科学转化医学》杂志上。

病例分享:肝移植术后严重贫血一例

王先生,50岁,汉族,肝移植术后1月余,乏力、头昏1周,入院治疗。

Gastroenterology:新机制抗乙肝药物疗效优于恩替卡韦

研究发现,NVR3-778在模型中表现出高效持久的抗HBV病毒效果,NVR3-778联合干扰素的抗病毒效果优于恩替卡韦

Hepatology:HBV pgRNA可用于乙肝相关肝癌的肿瘤分型和预后预测

【据《Journal of Hepatology》2017年12月报道】题:HBV pgRNA可用于乙肝相关肝癌的肿瘤分型和预后预测(作者Boris Halgand 等)