Science:重磅,老药新用,只需6天减少99%新冠病毒载量,还可作为光谱抗病毒药

2021-07-22 “E药世界”公众号 “E药世界”公众号

2021年7月20日,芝加哥大学等机构的研究人员在国际顶尖学术期刊 Science 发表了题为:Masitinib is a broad coronavirus 3CL inhibitor that

新型冠状病毒肺炎(COVID-19)疫情自2019年底暴发以来,仍在全球范围内蔓延,截至目前,全球已累计报告逾1.9亿例COVID-19确诊病例,逾411万名患者死亡,给全人类造成了巨大灾难。

针对COVID-19,除了加快疫苗接种工作外,寻找更安全有效的治疗方案同样非常迫切。由于疫情紧急,筛选已上市药物用于治疗和预防新冠,是一个很好的选择。

2021年7月20日,芝加哥大学等机构的研究人员在国际顶尖学术期刊 Science 发表了题为:Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2(马赛替尼是一种广泛的冠状病毒 3CL 抑制剂,可阻断 SARS-CoV-2 的复制)的研究论文。

研究团队利用“老药新用”的策略,从1900种已经安全使用的药物中发现了masitinib(马赛替尼),该药物是一种口服的酪氨酸激酶抑制剂,能够竞争性抑制新冠病毒的主要蛋白酶 3CLpro 的活性,从而抑制新冠病毒的复制。

小鼠体内实验表明,马赛替尼治疗只需6天就能将小鼠肺部和鼻子中的新冠病毒滴度降低为原来的1%以下,并且肺部炎症也有所减轻。此外,马赛替尼在体外实验中对新冠α、β、γ突变株同样有效。

研究团队对一个包含1900中已安全使用的药物库进行筛选,发现了其中有20种药物可以在体外实验中有效抑制新冠病毒的复制。其中8种药物能够有效抑制新冠病毒的主要蛋白酶 3CLpro 的活性,其中最有效的是一个名为masitinib(马赛替尼)的药物,它是一种口服的酪氨酸激酶抑制剂。

进一步研究发现,马赛替尼是 3CLpro 的竞争性抑制剂。

为了评估马赛替尼对感染新冠病毒后的治疗效果,研究团队用 2×10E4 PFU 的新冠病毒鼻内感染了20只K18-hACE2转基因小鼠。一半用PBS治疗作为对照组,另一半用马赛替尼(25 mg/kg)治疗,每天两次,从感染后12小时开始,持续10天。

实验结果表明,马赛替尼迅速有效地降低了小鼠体内的新冠病毒载量(在第 6 天降低了 99% 以上的病毒载量),且安全性良好,还减少了炎症特征,并显示出对生存和临床评分的潜在益处。值得注意的是,体外实验表明,马赛替尼对新冠α、β、γ突变株同样有效。

针对新冠病毒3CLpro的药物是一种有吸引力的治疗选择,部分原因是3CLpro被认为不太容易受到新冠病毒耐药性影响。马赛替尼是3CLpro的竞争性抑制剂,这种直接作用的抗病毒作用机制将马赛替尼与许多其他新冠治疗药物(包括聚合酶抑制剂或单克隆抗体)区分开来。

最后,研究团队表示,研究数据表明,马赛替尼在感染的早期最有益,能够产生最大抗病毒效果。口服马赛替尼是早期治疗的有潜力的策略。未来开发具有较低抗酪氨酸激酶活性的马赛替尼类似物将有利于减少其报告的副作用。

此外,马赛替尼除了能有效抑制新冠病毒及其突变株以外,还对多种冠状病毒和小RNA病毒有效,具有治疗其他病毒感染疾病的潜力,可作为一种广谱抗病毒药物。

原始出处:

Nir Drayman, et al. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science 20 Jul 2021: eabg5827. DOI: 10.1126/science.abg5827

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    2021-07-23 yahu
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    2021-07-23 jichang
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    2021-07-23 xxxx1054
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    2021-07-23 小小医者

    #马赛替尼#能有效抑制#新冠病毒#,是典型的#老药新用#

    0

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    2021-07-22 公卫新人

    新冠肺炎,疫情何时才能消失

    0

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