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

Bingbing Wang,Qingyou Xia,Qiang Sun,Yumei Wang,Liang Jiang,Enyu Xie,Huizhen Guo

doi:10.3390/molecules24071260

Abstract

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.

Highlights

The silkworm is an important economic insect for silk production
Simultaneous overexpression of antiviral genes and knock-down of viral genes improves the resistance of transgenic silkworms [8]
Transgenic expression of Cas9 and gRNAs targeting the B. mori nucleopolyhedrovirus (BmNPV) genes inhibits BmNPV in silkworms [9]

Summary

Introduction

The silkworm is an important economic insect for silk production. Silkworm diseases cause serious economic losses in sericulture. There is a need for antiviral agents in sericulture. Breeding antiviral silkworm strains using transgenic technology is an approach employed for virus control [1]. Overexpression of Bmlipase-1 inhibits BmNPV during the initial infection stage [2]. Overexpression of hycu-ep inhibits viral protein synthesis [6]. Regulation of host immunity via overexpression of PGRPs enhances the antiviral capacity of silkworms [1,7]. Simultaneous overexpression of antiviral genes and knock-down of viral genes improves the resistance of transgenic silkworms [8]. Transgenic expression of Cas and gRNAs targeting the BmNPV genes inhibits BmNPV in silkworms [9]. A safety assessment of transgenic silkworms has to be performed before commercialization

Methods

Results

Conclusion