BX795, a kinase inhibitor, inhibit duck plague virus infection via targeting US3 kinase.

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.

• Authors: 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
• Journal: Poultry science (Poult Sci) Vol. 102 Issue 5 Pg. 102597 (May 2023) ISSN: 1525-3171 [Electronic] England
• PMID: 36931072 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• BX795
• Antineoplastic Agents
• Antiviral Agents

Topics

• Animals
• Ducks
• Chickens
• Antineoplastic Agents
• Antiviral Agents (pharmacology)