Development of a novel fluorogenic assay method for screening inhibitors of bovine leukemia virus protease and identification of mitorubrinic acid as an anti-BLV compound

被引：1

作者：

Murakami, Hironobu ^{[1
,2
]}

Fujikawa, Yuuta ^{[3
]}

Mori, Masaya ^{[3
]}

Mosu, Nozomi ^{[1
]}

Taguchi, Akihiro ^{[4
]}

Hayashi, Yoshio ^{[4
]}

Inoue, Hideshi ^{[3
]}

Kamisuki, Shinji ^{[1
,2
]}

机构：

[1] Azabu Univ, Sch Vet Med, Sagamihara, Kanagawa, Japan

[2] Azabu Univ, Ctr Human & Anim Symbiosis Sci, Sagamihara, Kanagawa, Japan

[3] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Hachioji, Tokyo, Japan

[4] Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo, Japan

来源：

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY | 2023年 / 87卷 / 09期

基金：

日本学术振兴会;

关键词：

fluorogenic assay; protease inhibitor; bovine leukemia virus; mitorubrinic acid; MILK-PRODUCTION; INFECTION; PRODUCTIVITY; ASSOCIATION; FUNGUS;

D O I：

10.1093/bbb/zbad073

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a fatal cattle disease that leads to significant economic losses in the livestock industry. Currently, no effective BLV countermeasures exist, except testing and culling. In this study, we developed a high-throughput fluorogenic assay to evaluate the inhibitory activity of various compounds on BLV protease, an essential enzyme for viral replication. The developed assay method was used to screen a chemical library, and mitorubrinic acid was identified as a BLV protease inhibitor that exhibited stronger inhibitory activity than amprenavir. Additionally, the anti-BLV activity of both compounds was evaluated using a cell-based assay, and mitorubrinic acid was found to exhibit inhibitory activity without cytotoxicity. This study presents the first report of a natural inhibitor of BLV protease-mitorubrinic acid-a potential candidate for the development of anti-BLV drugs. The developed method can be used for high-throughput screening of large-scale chemical libraries. [GRAPHICS] .

引用

页码：946 / 953

页数：8