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

Journal Article (Journal Article)

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).

Full Text

Duke Authors

Cited Authors

  • Drayman, N; DeMarco, JK; Jones, KA; Azizi, S-A; Froggatt, HM; Tan, K; Maltseva, NI; Chen, S; Nicolaescu, V; Dvorkin, S; Furlong, K; Kathayat, RS; Firpo, MR; Mastrodomenico, V; Bruce, EA; Schmidt, MM; Jedrzejczak, R; Muñoz-Alía, MÁ; Schuster, B; Nair, V; Han, K-Y; O'Brien, A; Tomatsidou, A; Meyer, B; Vignuzzi, M; Missiakas, D; Botten, JW; Brooke, CB; Lee, H; Baker, SC; Mounce, BC; Heaton, NS; Severson, WE; Palmer, KE; Dickinson, BC; Joachimiak, A; Randall, G; Tay, S

Published Date

  • August 20, 2021

Published In

Volume / Issue

  • 373 / 6557

Start / End Page

  • 931 - 936

PubMed ID

  • 34285133

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.abg5827

Language

  • eng

Conference Location

  • United States