三磷酸腺苷类似物可有效抑制寨卡病毒的RNA依赖性RNA聚合酶。
Adenosine triphosphate analogs can efficiently inhibit the Zika virus RNA-dependent RNA polymerase.
作者信息
Hercík Kamil, Kozak Jaroslav, Šála Michal, Dejmek Milan, Hřebabecký Hubert, Zborníková Eva, Smola Miroslav, Ruzek Daniel, Nencka Radim, Boura Evzen
机构信息
Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2, 166 10 Prague 6, Czechia.
Veterinary Research Institute, Hudcova 70, CZ-62100 Brno, Czechia; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005 Ceske Budejovice, Czechia.
出版信息
Antiviral Res. 2017 Jan;137:131-133. doi: 10.1016/j.antiviral.2016.11.020. Epub 2016 Nov 27.
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity. Our results suggest that the traditional 2'-C-methylated nucleosides pursued in the race for anti-HCV treatment can be superseded by brand new scaffolds in the case of the Zika virus.
我们描述了一种活性重组寨卡病毒RNA依赖性RNA聚合酶（RdRp）的表达与纯化。接下来，我们展示了一种用于测量其活性的体外检测方法的开发与优化。然后，我们将该检测方法应用于选定的三磷酸类似物，发现2'-C-甲基化核苷具有很强的抑制活性。令人惊讶的是，碳水化合物锁定在类似“北”构象的碳环衍生物以及具有“南”构象的核糖核苷酸也表现出很强的活性。我们的结果表明，在抗丙型肝炎病毒治疗竞争中所追求的传统2'-C-甲基化核苷，在寨卡病毒的情况下可能会被全新的骨架所取代。
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