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

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...

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Autores principales: Wang, Bingbing, Jiang, Liang, Guo, Huizhen, Sun, Qiang, Wang, Yumei, Xie, Enyu, Xia, Qingyou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480691/
https://www.ncbi.nlm.nih.gov/pubmed/30939726
http://dx.doi.org/10.3390/molecules24071260
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author Wang, Bingbing
Jiang, Liang
Guo, Huizhen
Sun, Qiang
Wang, Yumei
Xie, Enyu
Xia, Qingyou
author_facet Wang, Bingbing
Jiang, Liang
Guo, Huizhen
Sun, Qiang
Wang, Yumei
Xie, Enyu
Xia, Qingyou
author_sort Wang, Bingbing
collection PubMed
description 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.
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spelling pubmed-64806912019-04-30 Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus Wang, Bingbing Jiang, Liang Guo, Huizhen Sun, Qiang Wang, Yumei Xie, Enyu Xia, Qingyou Molecules Article 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. MDPI 2019-04-01 /pmc/articles/PMC6480691/ /pubmed/30939726 http://dx.doi.org/10.3390/molecules24071260 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Bingbing
Jiang, Liang
Guo, Huizhen
Sun, Qiang
Wang, Yumei
Xie, Enyu
Xia, Qingyou
Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title_full Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title_fullStr Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title_full_unstemmed Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title_short Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus
title_sort screening of pi3k-akt-targeting drugs for silkworm against bombyx mori nucleopolyhedrovirus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480691/
https://www.ncbi.nlm.nih.gov/pubmed/30939726
http://dx.doi.org/10.3390/molecules24071260
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