Poultry Science (May 2023)
BX795, a kinase inhibitor, inhibit duck plague virus infection via targeting US3 kinase
- Yanming Tian,
- Bin Tian,
- Mingshu Wang,
- Dongjie Cai,
- Anchun Cheng,
- Wei Zhang,
- Ying Wu,
- Qiao Yang,
- Xuming Ou,
- Di Sun,
- Shaqiu Zhang,
- Sai Mao,
- XinXin Zhao,
- Juan Huang,
- Qun Gao,
- Dekang Zhu,
- Renyong Jia,
- Shun Chen,
- Mafeng Liu
Affiliations
- Yanming Tian
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Bin Tian
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Mingshu Wang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Dongjie Cai
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Anchun Cheng
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Corresponding author:
- Wei Zhang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan 611130, PR China
- Ying Wu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Qiao Yang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Xuming Ou
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Di Sun
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Shaqiu Zhang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Sai Mao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- XinXin Zhao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Juan Huang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Qun Gao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Dekang Zhu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Renyong Jia
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Shun Chen
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Mafeng Liu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan 611130, PR China
- Journal volume & issue
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Vol. 102,
no. 5
p. 102597
Abstract
ABSTRACT: Duck plague virus (DPV) is a typical DNA virus of waterfowl, it causes huge economic losses to the duck industry due to the higher mortality and lower egg production. The disease is one of the frequent epidemics and outbreaks on duck farms because present vaccines could not provide complete immunity and there are no specific antiviral drugs available. Therefore, the development of antiviral drugs is urgently needed. In this study, we evaluated the antiviral activity of BX795, a specific kinase inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), protein kinase B (AKT) and Tank binding kinase 1 (TBK1), against DPV in different duck cells. Our study demonstrated that BX795 reveals prominent antiviral activity in a dose-dependent manner in different types of duck cells. Time-addition and antiviral duration analysis uncovered that BX795 inhibits viral infection therapeutically and its antiviral activity lasts longer than 96 h. Further studies have shown that BX795 prevents cell-to-cell spread of the DPV rather than affects other stage of viral life cycle. Mechanistically, BX795 can inhibit DPV US3 kinase activity, reduce the phosphorylation of US3 substrates, and prevent the interaction between US3 and UL47. Taking together, our study demonstrated BX795, which disrupts the viral kinase activity, is a candidate antiviral agent for DPV.
