一种由人类基因组编码的自然存在的抗病毒核酸
Anthony S Gizzi1, Tyler L Grove2, Jamie J Arnold3
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA.
Nature
|June 22, 2018
概括
维佩林是一种干扰素诱导蛋白,产生一种名为3'-脱氧-3',4'-二-CTP (ddhCTP) 的新分子. 这种分子通过作为链终结器,自然抑制病毒复制,为病毒提供新的治疗策略.
科学领域:
- 生物化学
- 病毒学
- 分子生物学
背景情况:
- 病毒感染带来了重大的公共卫生挑战,需要对病毒生命周期进行更深入的了解,以便开发新的治疗方法.
- 众所周知,维佩林是一种激进的S- 腺- L- 甲 (SAM) 酶,可以抑制广泛的RNA和DNA病毒.
- 其广泛的抗病毒活性与众多宿主和病毒蛋白相互作用.
研究的目的:
- 阐明维珀林抗病毒作用的酶机制.
- 确定维珀林产生的特定分子及其在病毒抑制中的作用.
- 研究这种机制在开发新的抗病毒疗法方面的潜力.
主要方法:
- 酶测试以描述viperin的催化活性.
- 质谱测量以确定反应产物.
- 使用各种flavivirus进行RNA依赖RNA聚合酶 (RdRp) 测定.
- 使用寨卡病毒模型的体内研究.
主要成果:
- 维佩林催化了三酸 (CTP) 转化为3 - 脱氧-3 - 二酸 (ddhCTP).
- 哺乳动物细胞和IFNα刺激的巨细胞产生大量的ddhCTP.
- ddhCTP 作为 Flavivirus RdRps 的链终结剂,并在体内直接抑制寨卡病毒的复制.
结论:
- 维佩林的抗病毒机制涉及产生一种自然存在的复制链终结体,ddhCTP.
- 这一发现为viperin广泛的抗病毒作用提供了统一的解释.
- 维佩林的酶活性和由此产生的ddhCTP是抗病毒药物开发的有希望的目标.
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