病毒RNA降解：治疗SARS-CoV-2感染的新方法

COVID-19疫苗的开发速度很快，但变种病毒的出现迫使科学家经常修改治疗方法。理想情况下，治疗方法应该针对突变抗性病毒蛋白，但这已被证明是困难的。不过，报导在ACS Central Science的研究人员现在开发出一种直接针对并降解病毒RNA基因组的系统，减少了小鼠的感染。这种方法还可以适用于对抗许多病毒和治疗各种疾病。

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疫苗和抗病毒药物通常针对对病毒感染和复制至关重要的蛋白进行作用。然而，这种作用会导致病毒进行突变，减少现有治疗方法的效力，需要开发新的疫苗和药物。

为了解决这个问题，研究人员进行了针对病毒RNA基因组内高度保守的结构进行作用的研究。其他研究小组通过将小分子RNA结合剂连接到核酸酶L配体（RIBOTACs）上，创建了依赖于细胞内核酸酶表达的降解剂，这在组织中有所不同。

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为了避免这种依赖性，Gonçalo J. L. Bernardes，Konstantinos Tzelepis，Sigitas Mikutis和他们的同事发现将咪唑并连接到RNA可以降解核酸。因此，他们想知道将咪唑连接到一种RNA结合分子上是否会产生有针对性的降解作用。

为了实现这种方法，团队使用与G四聚体（G4）RNA结构结合的吡啶哌唑（PDS）和与β冠状病毒假编码结构结合的MTDB作为RNA结合分子。然后，研究人员给这些化合物加上了一个柔性的连接器和咪唑，称这些分子为近距离诱导核酸降解剂（PINADs）。通过将咪唑带到近距离的RNA中，两种PINADs都可以降解SARS-CoV-2 RNA。

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此外，这些化合物在感染SARS-CoV-2及其α和δ变异株的细胞中测试时也具有显著的效果。重要的是，当研究人员将MTDB降解剂给被SARS-CoV-2感染的小鼠时，病毒载量降低了，病毒感染和复制的生物标记物也降低了。

研究人员表示，他们的

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