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鉴定FDA批准的抑制SARS-CoV-2和人类诺罗病毒复制的药物

Tsuyoshi Hayashi¹, Junki Hirano², Kosuke Murakami^1,3

¹Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.

Biological & pharmaceutical bulletin

|July 9, 2025

概括

这项研究选了FDA批准的药物,以找到SARS-CoV-2抑制剂. 几种药物有效抑制了SARS-CoV-2和人类诺罗病毒的复制,提供了潜在的新疗法.

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:

严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 构成了全球健康的重大威胁.
向病毒蛋白酶是开发抗病毒疗法的关键策略.
识别现有的药物用于重新使用可以加速治疗的发展.

研究的目的:

通过准其3CL蛋白酶 (3CLpro) 来抑制SARS-CoV-2复制的美国食品和药物管理局 (FDA) 批准的药物.
评估针对SARS-CoV-2和人类诺罗病毒 (HuNoV) 的已识别化合物的抗病毒活性.

主要方法:

使用基于细胞和绿色光蛋白 (GFP) 记者测试 (FlipGFP-3CLpro测试) 来评估3CLpro活性,对FDA批准的药物库进行选.
实验室酶分析和基于细胞的分析被用来验证化合物对SARS-CoV-2的疗效.
人类肠道器官被用于测试对HuNoV.病毒的抗病毒作用.

主要成果:

五种FDA批准的药物 (auranofin,endoxifen,netupitant,pimozide和regorafenib) 被确定为成功的药物.
三种化合物 (auranofin,endoxifen和pimozide) 在体外显示了3CLpro活性的剂量依赖抑制.
这五种化合物都抑制了SARS-CoV-2在培养细胞中的复制.
这五种化合物中有四种在人类肠道有机体中显著抑制了HuNoV复制.

结论:

几种FDA批准的药物显示出作为SARS-CoV-2复制抑制剂的潜力.
一些已识别的化合物也对人类诺罗病毒表现出活性,这表明具有广泛的抗病毒潜力.
这些发现需要进一步研究,以开发新型抗病毒疗法.

关键词:

翻转GFP测试方法复合屏幕是一个复合屏幕.人类诺罗病毒人类诺罗病毒严重急性呼吸系统综合征新冠病毒2 病毒蛋白酶是一种病毒蛋白酶.

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