Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2

doi:10.1126/science.abg5827

GSTDTAP > 气候变化

DOI	10.1126/science.abg5827
	Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2
	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
	2021-08-20
发表期刊	Science
出版年	2021
英文摘要	Inside host cells, the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is translated into two polyproteins that are cleaved to yield the individual viral proteins. The main viral protease, known as Mpro or 3CLpro, plays a key role in these cleavages, making it an important drug target. Drayman et al. identified eight drugs that target 3CLpro from a library of 1900 clinically safe drugs. Because of the challenge of working with SARS-CoV-2, they started by screening for drugs that inhibit the replication of a human coronavirus that causes the common cold. They then evaluated the top hits for inhibiting SARS-CoV-2 replication and for inhibiting 3CLpro. Masitinib, a broad antiviral, inhibited the main proteases of coronaviruses and picornaviruses and was effective in reducing SARS-CoV-2 replication in mice. Science , abg5827, this issue p. [931][1] There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 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 cultured human cells. 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]: /lookup/doi/10.1126/science.abg5827
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：151[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/336038
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Nir Drayman,Jennifer K. DeMarco,Krysten A. Jones,et al. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2[J]. Science,2021.
APA	Nir Drayman.,Jennifer K. DeMarco.,Krysten A. Jones.,Saara-Anne Azizi.,Heather M. Froggatt.,...&Savaş Tay.(2021).Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.Science.
MLA	Nir Drayman,et al."Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2".Science (2021).