| Literature DB >> 34285133 |
Nir Drayman1, Jennifer K DeMarco2, Krysten A Jones3,4, Saara-Anne Azizi5,4, Heather M Froggatt6,7, Kemin Tan8,7,9,10, Natalia Ivanovna Maltseva3,7,9,10, Siquan Chen3,11, Vlad Nicolaescu3, Steve Dvorkin3,3, Kevin Furlong3, Rahul S Kathayat3,4, Mason R Firpo12,13, Vincent Mastrodomenico13, Emily A Bruce11,8,14, Madaline M Schmidt8,14, Robert Jedrzejczak7,9,10, Miguel Á Muñoz-Alía15,15, Brooke Schuster3,12, Vishnu Nair3,12, Kyu-Yeon Han2,5, Amornrat O'Brien16,13, Anastasia Tomatsidou8,3, Bjoern Meyer6, Marco Vignuzzi10,6, Dominique Missiakas3,3, Jason W Botten11,8,14,17, Christopher B Brooke14,18,19, Hyun Lee17,16, Susan C Baker6,12,13, Bryan C Mounce6,20,13, Nicholas S Heaton6,7, William E Severson4,2, Kenneth E Palmer18,2, Bryan C Dickinson3,4, Andrzej Joachimiak7,19,9,10,20, Glenn Randall19,3, Savaş Tay21,12.
Abstract
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).Entities:
Mesh：
Substances：
Year: 2021 PMID： 34285133 PMCID： PMC8809056 DOI： 10.1126/science.abg5827
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714