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筛选针对家蚕核多角体病毒的 PI3K-Akt 靶向药物。

Screening of PI3K-Akt-targeting Drugs for Silkworm against Nucleopolyhedrovirus.

机构信息

Biological Science Research Center, Southwest University, Chongqing 400716, China.

Chongqing Key Laboratory of Sericultural Science, Chongqing 400716, China.

出版信息

Molecules. 2019 Apr 1;24(7):1260. doi: 10.3390/molecules24071260.

Abstract

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.

摘要

核多角体病毒(BmNPV)是对家蚕最普遍的威胁。因此,养蚕业需要抗病毒药物。PI3K-Akt 通路对于杆状病毒的有效复制至关重要。为了筛选抗 BmNPV 的抗病毒药物,我们总结了针对 PI3K-Akt 的商业化合物,并选择了以下七种口服药物进行进一步分析:afuresertib、AZD8835、AMG319、HS173、AS605240、GDC0941 和 BEZ235。细胞活力测定显示,这些药物在 10µM 浓度下的细胞毒性并不强。病毒荧光观察和 qPCR 分析表明,这些候选药物显著抑制了 BmE 细胞中的 BmNPV。只有 AMG319 和 AZD8835 抑制了家蚕幼虫中的病毒增殖。经 AZD8835 处理的家蚕死亡率低于对照家蚕。Western blot 显示,AMG319 和 AZD8835 在 BmNPV 感染后降低了 p-Akt 的表达。这些结果表明,AZD8835 在养蚕业中有应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c56/6480691/1bcf66068673/molecules-24-01260-g001.jpg

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