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 NairKyu-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

Research output: Contribution to journalArticlepeer-review


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).

Original languageEnglish (US)
Article numbereabg5827
Pages (from-to)931-936
Number of pages6
Issue number6557
Early online dateJul 20 2021
StatePublished - Aug 20 2021


  • COVID-19
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

ASJC Scopus subject areas

  • General


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