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对肠道病毒D68的囊抑制剂的合理设计和体内验证
Kan Li1, Michael J Rudy2, Thomas Klose3
1Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Nature communications
|February 10, 2026
概括
新的抗病毒药物Jun11787和Jun11695在治疗D68肠道病毒 (EV-D68) 感染方面表现有前途. 这些化合物有效地降低了病毒载量,并预防了小鼠的,为未来治疗提供了希望.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 结构生物学 结构生物学
背景情况:
- 肠道病毒D68 (EV-D68) 是一个重要的呼吸道病原体.
- EV-D68感染可能导致严重的神经并发症,包括急性软骨髓炎 (AFM) 和儿童死亡.
- 目前,没有针对EV-D68.8的特定疫苗或抗病毒疗法.
研究的目的:
- 设计和开发针对EV-D68.8的新型抗病毒药物.
- 评估基于结构的设计抑制剂对EV-D68.8的体外和体内疗效.
- 研究这些抑制剂在EV-D68相关性脑膜炎的小鼠模型中的治疗潜力.
主要方法:
- 基于结构的药物设计使用冷电子显微镜 (Cryo-EM).
- 在体外抗病毒测试以确定对各种肠道病毒菌株的有效性.
- 在新生小鼠模型中进行体内研究,以评估治疗疗效,包括减少病毒位数,预防和体重增加.
主要成果:
- 两种新型化合物Jun11787和Jun11695被确定为EV-D68.8的强有力的抑制剂.
- 这些化合物与VP1囊蛋白的疏水峡谷区域结合.
- Jun11787和Jun11695证明了对多个EV-D68菌株的纳米分子功效,以及对EV-A71和CVB3的微分子功效.
- 在体内,Jun11787和Jun11695的治疗显著降低了脊髓病毒载量,预防了,并改善了受感染小鼠的体重增加,即使在感染后几天服用.
结论:
- Jun11787和Jun11695是针对EV-D68的有效抗病毒药物,具有广谱潜力.
- 这些化合物代表了对治疗EV-D68感染和相关的神经并发症的有前途的治疗方法.
- 基于结构的设计是开发针对具有挑战性的病毒病原体的新型抗病毒疗法的可行策略.
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