一种小分子融合抑制剂的流感病毒是口服活跃在小鼠
Maria J P van Dongen1,2, Rameshwar U Kadam3, Jarek Juraszek4
1Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, Archimedesweg 6, Leiden, Netherlands. mvandon@its.jnj.com wilson@scripps.edu.
研究人员开发出模仿广泛中和抗体 (bnAbs) 的小分子,以向流感血凝素 (HA) 干. 这些口服化合物可以中和A型流感病毒,并防止感染,从而提供一种潜在的新疗法.
科学领域:
- 病毒学
- 免疫学
- 药物发现
背景情况:
- 针对保存的血凝素 (HA) 干的广泛中和抗体 (bnAbs) 是通用流感疫苗和治疗药物的前景.
- 目前的bnAb开发面临着口头传递的挑战,需要替代策略.
研究的目的:
- 设计和优化复制抗干bnAbs的中和功能的小分子.
- 评估这些小分子作为口服流感治疗药物的疗效.
主要方法:
- 基于抗干bnAb CR6261的小分子的结构引导选择和优化.
- 针对血凝素 (HA) 中介融合的体外中和试验.
- 在流感感染的小鼠模型中进行的体内疗效研究.
- 使用差异化人类支气管上皮细胞的3D细胞培养模型.
主要成果:
- 通过抑制HA介导的融合,小分子化合物有效中和1组流感病毒.
- 这种化合物的口服保护了小鼠免受致命和次致命的流感挑战.
- 该化合物在人类支气管上皮细胞模型中证明了流感感染的中和.
- 结晶结构证实该化合物模仿HA干中的关键bnAb相互作用.
结论:
- 小分子可以被设计成模仿bnAb功能对抗流感HA干.
- 口服的小分子向HA干是流感治疗的可行策略.
- 这种方法为基于抗体的流感治疗提供了一个有希望的替代方案.
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