Bruton's tyrosine kinase inhibitor BTKi-2 inhibits mpox virus and vaccinia virus infection

IF 4.7 3区医学 Q1 Medicine

Virologica Sinica Pub Date : 2026-06-01 Epub Date: 2026-06-19 DOI:10.1016/j.virs.2026.06.011

Chen Yang, Runchu Zhao, Shuting Huo, Yaqing Zhang, Jingxi Feng, Mingli Gong, Lin Zhu, Conggang Zhang, Linqi Zhang, Jing Xue, Rong Zhang, Qihui Wang, Qiang Ding

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引用次数: 0

Abstract

The recent global outbreak of mpox virus (MPXV) infections underscores the urgent need for antiviral therapies against orthopoxviruses. In this study, using a high-content screening (HCS) platform based on a modified vaccinia virus Tiantan strain with GFP insertion (MVTT-GFP) under BSL-2 conditions, we screened 1513 kinase inhibitors for antiviral activity. Among these, Bruton's tyrosine kinase inhibitor BTKi-2 emerged as a potent candidate, exhibiting IC₅₀ of 0.535 μM against vaccinia virus (VACV) and 0.260 μM against MPXV in vitro, while maintaining low cytotoxicity. In a murine model of VACV-induced pneumonia, BTKi-2 treatment reduced lung viral loads by 90% and a significantly improved survival compared to vehicle-treated controls. Notably, mechanistic studies indicate that BTKi-2's antiviral effects cannot be completely attributed to the inhibition of BTK or EGFR/ErbB2 signaling. These findings highlight BTKi-2 as a promising antiviral agent in vitro and in vivo, suggesting that BTKi-2 may offer a potential avenue for future therapeutic development against orthopoxvirus infections.

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布鲁顿酪氨酸激酶抑制剂BTKi-2抑制痘病毒和牛痘病毒感染。

最近全球爆发的痘病毒（MPXV）感染强调了迫切需要针对正痘病毒的抗病毒治疗。本研究在BSL-2条件下，利用高含量筛选（HCS）平台，对带有GFP插入的改良痘苗病毒天坛株（MVTT-GFP）进行了抗病毒活性筛选。其中，布鲁顿酪氨酸激酶抑制剂BTKi-2是一种有效的候选药物，在体外对牛痘病毒（VACV）的IC50为0.535 μM，对MPXV的IC50为0.260 μM，同时保持较低的细胞毒性。在vacv诱导的肺炎小鼠模型中，BTKi-2治疗减少了90%的肺病毒载量，与载体治疗的对照组相比，显著提高了生存率。值得注意的是，机制研究表明，BTKi-2的抗病毒作用不能完全归因于抑制BTK或EGFR/ErbB2信号。这些发现强调了BTKi-2在体内和体外都是一种很有前景的抗病毒药物，表明BTKi-2可能为未来治疗正痘病毒感染提供一条潜在的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virologica Sinica Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

7.70

自引率

1.80%

发文量

3149

期刊介绍： Virologica Sinica is an international journal which aims at presenting the cutting-edge research on viruses all over the world. The journal publishes peer-reviewed original research articles, reviews, and letters to the editor, to encompass the latest developments in all branches of virology, including research on animal, plant and microbe viruses. The journal welcomes articles on virus discovery and characterization, viral epidemiology, viral pathogenesis, virus-host interaction, vaccine development, antiviral agents and therapies, and virus related bio-techniques. Virologica Sinica, the official journal of Chinese Society for Microbiology, will serve as a platform for the communication and exchange of academic information and ideas in an international context. Electronic ISSN: 1995-820X; Print ISSN: 1674-0769