Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2
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).
On January 2020, SARS-CoV-2 was identified as the causative agent of a new respiratory syndrome that was later named Corona Virus Disease 19 (COVID-19) (1). The virus has rapidly spread throughout the world, causing an ongoing pandemic, with millions of deaths (2). SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, single-strand, positive-sense RNA viruses (3). This family is composed of both human and animal pathogens, including two other emerging human pathogens (SARS-CoV and MERS-CoV) as well four endemic human viruses that are the second most common cause of the common cold (HCoV-OC43, 229E, NL63 and HKU1) (4).
