In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a global health problem. Despite the current implementation of COVID-19 vaccination schedules, identifying effective antiviral drug treatments for this disease continues to be a priority. A recent study showed that masitinib (MST), a tyrosine kinase inhibitor, blocks the proteolytic activity of SARS-CoV-2 main protease (M ). Although MST is a potential candidate for COVID-19 treatment, a comprehensive analysis of its interaction with M has not been done. In this work, we performed molecular dynamics simulations of the MST-M complex crystal structure. The effect of the protonation states of M H163 residue and MST titratable groups were studied. Furthermore, we identified the MST substituents and M mutations that affect the stability of the complex. Our results provide valuable insights into the design of new MST analogs as potential treatments for COVID-19.