皮里米丁抑制剂与核酸相似物协同阻断SARS-CoV-2
David C Schultz1, Robert M Johnson2, Kasirajan Ayyanathan3
1Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA. dschultz@pennmedicine.upenn.edu.
Nature
|February 7, 2022
概括
研究人员对18000种针对SARS-CoV-2的药物进行了查,发现了122种具有抗病毒活性. 结合核酸相似物与皮里米丁抑制剂显示出对COVID-19的协同效应,提供了一个有前途的治疗策略.
科学领域:
- 病毒学
- 药物发现
- 分子生物学
背景情况:
- 在全球范围内,SARS-CoV-2 已造成数百万人的死亡,除了疫苗之外,还需要有效的抗病毒治疗.
- 新出现的变种构成威胁,需要开发能够克服疫苗规避的新疗法.
- 目前对COVID-19的治疗选择有限,这凸显了广泛的抗病毒药物发现的紧迫性.
研究的目的:
- 检查大量的抗病毒药物对SARS-CoV-2的活性.
- 识别新型抗病毒化合物,特别是核酸相似物和向宿主的药物.
- 评估针对SARS-CoV-2感染的联合疗法的协同效应.
主要方法:
- 在人类呼吸系统细胞中使用活的SARS-CoV-2检查了大约18000种药物.
- 确定候选药物的抗病毒活性和选择性的验证.
- 在体外和体内测试皮里米丁生物合成抑制剂和核酸相应物的协同作用组合.
主要成果:
- 122种药物表现出对SARS-CoV-2的抗病毒活性和选择性.
- 在活性化合物中发现了16种核酸相似物,包括已批准的抗病毒药物,如雷梅西维尔和莫尔努皮拉维尔.
- 皮里米丁生物合成抑制剂和核酸相似剂的联合治疗显示出对SARS-CoV-2的协同抑制,包括对新兴菌株的抑制.
结论:
- 通过大规模查已经确定了大量针对SARS-CoV-2的潜在抗病毒药物.
- 针对宿主核酸生物合成途径是开发广泛抗病毒药物的可行策略.
- 现有和新型抗病毒药物的协同作用为管理COVID-19和潜在的未来病毒威胁提供了有希望的临床策略.
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