西克洛皮洛克斯通过向铁代谢来抑制波克斯病毒的复制
Anil Pant1, Djamal Brahim Belhaouari1, Lara Dsouza1
1Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Antiviral research
|October 9, 2025
概括
一种抗真菌药物Ciclopirox (CPX) 通过结合铁,有效抑制疫苗病毒 (VACV) 复制. 这种抗病毒活性扩展到其他正病毒,建议CPX作为潜在的治疗poxvirus感染.
科学领域:
- 病毒学 病毒学
- 抗菌研究 抗菌研究
- 药物发现 药物发现 药物发现
背景情况:
- 脊髓灰质炎病毒,包括疫苗病毒 (VACV),对全球健康构成重大威胁,推动了对新抗病毒疗法的需求.
- 高通量查确定了 FDA 批准的抗真菌药物 ciclopirox (CPX) 作为 VACV 复制的潜在抑制剂.
研究的目的:
- 描述环洛皮洛克斯 (CPX) 对疫苗病毒 (VACV) 的抗病毒活性和作用机制.
- 评估CPX对其他骨质疏松病毒和体外模型的疗效.
主要方法:
- 人类初级纤维细胞被用来评估CPX的抗病毒活性 (EC50) 和细胞毒性 (CC50).
- 用补充铁和过度表达铁依赖酶 (RRM2,F4L) 的救援实验阐明了它的作用机制.
- 在体外测试中对牛病毒和 (mpox) 病毒进行了测试,并使用了ex vivo小鼠肺组织来测试CPX的疗效.
主要成果:
- CPX 显示出强烈的 VACV 复制抑制 (亚微分子 EC50) 与低宿主细胞毒性 (CC50 > 500μM).
- 抗病毒作用主要归因于细胞内铁 (Fe3+和Fe2+) 的化.
- 在实验室中,CPX抑制了牛病毒和mopox病毒的复制,并在ex vivo小鼠肺组织中降低了VACV标位.
结论:
- 西克洛皮洛克斯 (CPX) 通过向宿主铁代谢,对形病毒表现出广泛的抗病毒活性.
- CPX是治疗包括mopox病毒在内的pox病毒感染的有希望的治疗候选者.
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