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Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus

机译:家蚕抗家蚕核多角体病毒PI3K-Akt靶向药物的筛选

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摘要

Bombyx mori nucleopolyhedrovirus (BmNPV) is the most prevalent threat to silkworms. Hence, there is a need for antiviral agents in sericulture. The PI3K-Akt pathway is essential for the efficient replication of the baculovirus. In an attempt to screen antiviral drugs against BmNPV, we summarized the commercial compounds targeting PI3K-Akt and selected the following seven oral drugs for further analyses: afuresertib, AZD8835, AMG319, HS173, AS605240, GDC0941, and BEZ235. Cell viability assay revealed that the cytotoxicity of these drugs at 10 µM concentration was not strong. Viral fluorescence observation and qPCR analysis showed that these candidate drugs significantly inhibited BmNPV in BmE cells. Only AMG319 and AZD8835 inhibited viral proliferation in silkworm larvae. The mortality of AZD8835-treated silkworms was lower than that of the control silkworms. Western blotting showed that AMG319 and AZD8835 decreased p-Akt expression after BmNPV infection. These results suggest that AZD8835 has application potential in sericulture.
机译:家蚕核多角体病毒(BmNPV)是对蚕的最普遍威胁。因此,在蚕桑中需要抗病毒剂。 PI3K-Akt途径对于杆状病毒的有效复制至关重要。为了筛选针对BmNPV的抗病毒药物,我们总结了靶向PI3K-Akt的商业化合物,并选择了以下7种口服药物进行进一步分析:阿富瑞替尼,AZD8835,AMG319,HS173,AS605240,GDC0941和BEZ235。细胞活力分析表明,这些药物在10 µM浓度下的细胞毒性不强。病毒荧光观察和qPCR分析表明,这些候选药物显着抑制了BmE细胞中的BmNPV。只有AMG319和AZD8835抑制家蚕幼虫中的病毒增殖。 AZD8835处理的家蚕的死亡率低于对照家蚕。蛋白质印迹显示,BmNPV感染后,AMG319和AZD8835降低了p-Akt表达。这些结果表明,AZD8835在蚕桑中具有应用潜力。

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