小分子PS10通过向HSP90和多个病毒非结构蛋白来抑制PRRSV复制
Yongjie Chen1, Jingxing Wang1, Haotong Lu1
1Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Animal Disease Control and Prevention, Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, , Guangzhou, Guangdong, People's Republic of China.
Journal of virology
|February 18, 2026
概括
一种新的化合物PS10通过向病毒蛋白和宿主因素,如HSP90.0,有效地抑制猪生殖和呼吸系统综合征病毒 (PRRSV) 复制. 这一发现为开发针对PRRSV的广泛抗病毒疗法提供了有前途的途径.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 免疫学 免疫学 免疫学
背景情况:
- 猪生殖和呼吸系统综合征病毒 (PRRSV) 对全球猪产量和粮食安全构成重大威胁.
- 现有的PRRSV疫苗往往对各种病毒株具有有限的交叉保护,因此需要开发替代治疗方法.
- PRRSV的遗传变异性使有效的疾病管理策略变得复杂.
研究的目的:
- 确定针对PRRSV复制的新型抗病毒化合物.
- 阐明已识别的抑制剂的作用机制.
- 评估新治疗药物控制PRRSV感染的潜力.
主要方法:
- 复合图书馆查以确定PRRSV抑制剂.
- 在细胞培养 (Marc-145细胞) 和初级猪膜巨细胞中进行抗病毒检测.
- 机理学研究包括热冲击蛋白90 (HSP90) 表达分析,细胞因子分析,病毒非结构蛋白质量化,分子对接和细胞热转移试验 (CETSA).
主要成果:
- 鉴定出2-[(2,4-二二氧化) 硫]异因多林-4,6-二醇 (PS10) 是PRRSV复制的一个强有力的抑制剂.
- PS10在不同的PRRSV菌株和宿主细胞中表现出剂量依赖的抗病毒活性,细胞毒性低.
- 通过直接结合,PS10抑制了PRRSV诱导的HSP90表达,减少了促炎性细胞因子的产生,并降低了病毒非结构蛋白 (nsp2,nsp3,nsp10,nsp11) 的水平.
结论:
- PS10是一种有前途的抗病毒药物,通过向关键的病毒和宿主因素,有效对抗PRRSV.
- 这项研究为PS10的机制提供了洞察力,包括它与病毒蛋白的相互作用和宿主反应的调制.
- PS10为开发针对PRRSV和潜在的其他病毒感染的新型,广泛的抗病毒疗法提供了潜在的基础.
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