体聚合混了基于细胞的Covid-19抗病毒屏幕
Isabella S Glenn1, Lauren N Hall1, Mir M Khalid2,3
1Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, California 94143, United States.
Journal of medicinal chemistry
|June 12, 2024
概括
候选药物中的体聚合可以在COVID-19抗病毒试验中引起假阳性. 减少聚合的治疗方法显著降低了药物的有效性,揭示了聚合是药物重用中的常见工件.
科学领域:
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
- 病毒学 病毒学
背景情况:
- 体聚合是早期药物发现中错误阳性的主要原因.
- 基于细胞的感染性测定对于识别抗病毒药物至关重要,特别是在治疗COVID-19等疾病的药物重新定位方面.
研究的目的:
- 为了研究SARS-CoV-2进入抑制剂中体聚合的作用,用于基于细胞的感染性测试.
- 评估聚合对候选药物的抗病毒功效测量的影响.
主要方法:
- 动态光散射被用来检测41种候选药物中的体颗粒形成.
- 药物悬浮被用BSA或离心处理以减轻聚合.
- 进行了尖端伪病毒感染性测定,以测量聚合缓解前后的抗病毒功效.
主要成果:
- 在41种候选药物中,有17种形成了体颗粒,并表现出洗剂依赖的酶抑制.
- 在BSA或离心处理后,抗病毒功效降低了至少10倍,表明基于聚合的机制.
- 光显微镜显示,聚合物隔离了标记的尖端蛋白,与人工相互作用一致.
结论:
- 体聚合是针对COVID-19的基于细胞的抗病毒药物重新定位试验中常见的工件.
- 用BSA进行预和离心,作为有效的反屏,用于识别和消除聚合诱导的工件.
- 解决状聚合对于准确评估抗病毒研究中的药物疗效至关重要.
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