Abstract

Antiviral activity of antisense oligodeoxyribonucleotides with phosphorothioate or mesyl phosphoramidate internucleotidic groups targeting the main capsid protein VP72 mRNA of the African swine fever virus (ASFV), either in a free form with Lipofectamine 3000 transfection or in the form of ionic complexes with amino-modified mesoporous silicon dioxide nanoparticles, has been evaluated in Vero cells infected with ASFV. Relatively high cytotoxicity of oligonucleotide nanocomplexes for Vero cells at concentrations above 500 nM was detected. Two sequences of antisense oligonucleotides were identified, which reduced the virus titer by an order of magnitude at 500 nM. The antiviral effect of nanocomplexes exceeded that of free oligonucleotides in the presence of Lipofectamine 3000, which indicates a more efficient delivery of nanocomplexes to the cells. Antisense oligonucleotides able to reduce the replication of ASFV were hitherto unknown from the literature. The obtained data can be used as a starting point for further research on the development of oligonucleotide-based antiviral drugs against the African swine fever virus.

中文翻译：

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靶向VP72蛋白的反义寡核苷酸纳米复合物在非洲猪瘟病毒感染的Vero细胞中的抗病毒活性。

摘要

反义寡脱氧核糖核苷酸与针对非洲猪瘟病毒（ASFV）的主要衣壳蛋白VP72 mRNA的硫代磷酸酯或氨基磷酸甲磺酸酯基核苷酸间基团的抗病毒活性，可以是Lipofectamine 3000转染的游离形式，也可以是具有氨基修饰的介孔离子复合物的形式二氧化硅纳米颗粒已经在感染ASFV的Vero细胞中进行了评估。检测到浓度高于500 nM的寡核苷酸纳米复合物对Vero细胞具有相对较高的细胞毒性。鉴定了两个反义寡核苷酸序列，它们在500 nM下将病毒效价降低了一个数量级。在Lipofectamine 3000的存在下，纳米复合物的抗病毒作用超过了游离寡核苷酸，这表明纳米复合物可以更有效地递送至细胞。迄今尚不知道能够减少ASFV复制的反义寡核苷酸。获得的数据可以用作进一步研究开发针对非洲猪瘟病毒的基于寡核苷酸的抗病毒药物的起点。