论文
论文标题：Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2
作者：Nir Drayman , Jennifer K. DeMarco , Krysten A. Jones , Saara-Anne Azizi , Heather M. Froggatt , Kemin Tan , Natalia Ivanovna Maltseva , Siquan Chen , Vlad Nicolaescu , Steve Dvorkin , Kevin Furlong , Rahul S. Kathayat , Mason R. Firpo , Vincent Mastrodomenico , Emily A. Bruce , Madaline M. Schmidt , Robert Jedrzejczak , Miguel Á. Muñoz-Alía , Brooke Schuster , Vishnu Nair , Kyu-yeon Han , Amornrat O’Brien , Anastasia Tomatsidou , Bjoern Meyer , Marco Vignuzzi , Dominique Missiakas , Jason W. Botten , Christopher B. Brooke , Hyun Lee , Susan C. Baker , Bryan C. Mounce , Nicholas S. Heaton , William E. Severson , Kenneth E. Palmer , Bryan C. Dickinson , Andrzej Joachimiak , Glenn Randall , Savaş Tay
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期刊：Science
发表时间：2021/07/20
数字识别码：10.1126/science.abg5827
摘要：There is an urgent need for antiviral agents that treat SARS-CoV-2 infection. We screened a library of 1,900 clinically safe drugs against OC43, a human beta-coronavirus that causes the common cold and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in vitro. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351 and P.1).
[1] Nir Drayman et al., (2021), Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2, Science, DOI: 10.1126/science.abg5827
[2] AB Science announces the publication of an article in the world-renowned journal Science that confirms potential of masitinib as a treatment of Covid-19 with anti-viral activity against SARS-CoV-2 and all tested variants of concern, Retrieved July 20, 2021, from https://www.globenewswire.com/ne ... al-activity-ag.html
Science：马赛替尼可抑制SARS-CoV-2病毒复制
2021年7月22日讯/生物谷BIOON/---在一项新的研究中，来自美国芝加哥大学等研究机构的研究人员发现药物马赛替尼（masitinib）可能对治疗COVID-19有效。虽然这种药物已经进行了几项治疗人类疾病的临床试验，尚未获得治疗人类疾病的批准，但是这些作者发现它可以抑制SARS-CoV-2在人类细胞培养物和小鼠模型中的复制，导致病毒载量大大降低。相关研究结果于2021年7月20日在线发表在Science期刊上，论文标题为“Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2”。
这些作者还发现这种药物对许多类型的冠状病毒和小RNA病毒（picornavirus）有效。由于其抑制病毒复制的方式，它还被证明在面对SARS-CoV-2变体时仍然有效。
论文通讯作者、芝加哥大学的Savas Tay教授说，“SARS-CoV-2主蛋白酶的抑制剂，如马赛替尼那样，可能是治疗COVID患者的一种新的潜在方法，特别是在疾病的早期阶段。COVID-19可能将伴随我们许多年，新的冠状病毒将继续出现。找到具有抗病毒特性的现有药物可能是治疗这些疾病的一个重要部分。”
