高通量查识别了广泛的冠状病毒进入抑制剂
Suman Khan1, Efrat Ozer Partuk1, Jeanne Chiaravalli2
1Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
iScience
|June 17, 2024
概括
研究人员选了超过20万个分子,以寻找新的抗病毒药物. 他们发现了新的小分子和一种衍生物,这些分子显示出对新出现的冠状病毒 (CoV) 具有潜在的广谱抑制剂的潜力.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 分子生物学分子生物学
背景情况:
- COVID-19大流行强调了对新出现的冠状病毒 (CoV) 有效的抗病毒药物的迫切需要.
- 抑制尖峰 (S) 糖蛋白介导的病毒进入是一种有前途的治疗策略.
- 针对病毒进入受体结合的下游是开发广谱抗病毒药物的关键.
研究的目的:
- 建立一个高通量查 (HTS) 平台,用于识别新冠病毒进入的小分子抑制剂.
- 选一个大型的小分子图书馆,以检测抑制SARS-CoV-2 S糖蛋白介导病毒进入的化合物.
- 发现针对新出现的冠状病毒有效的新型广谱抗病毒药物.
主要方法:
- 开发基于伪病毒的高通量查 (HTS) 平台.
- 对大约20万个小分子进行针对SARS-CoV-2 S携带伪病毒的查.
- 对MERS-CoV,SARS-CoV-2变种 (阿尔法,三角形,奥米克朗) 和真实的SARS-CoV-2进行反查和验证.
主要成果:
- 在反查后确定了65种SARS-CoV-2 S-特定抑制剂.
- 包括纳法莫斯塔特在内的五种化合物对MERS-CoV S携带的伪病毒表现出活性.
- 一种未报告的抑制剂及其衍生物证明了其作为针对SARS-CoV-2变种和真实病毒的广泛抗病毒药物的潜力.
结论:
- 开发的HTS平台有效地识别了冠状病毒进入抑制剂.
- 一种新型的抑制剂及其衍生品显示为广泛的抗病毒药物具有前途.
- 需要进一步验证,以探索这些化合物对新出现的CoVs的治疗潜力.
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