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

Martínez‐Ortega, Ulises; Figueroa‐Figueroa, Diego I.; Hernández‐Luis, Francisco; Aguayo‐Ortiz, Rodrigo

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(pro)). Although MST is a potential candidate for COVID‐19 treatment, a comprehensive analysis of its interaction with M(pro) has not been done. In this work, we performed molecular dynamics simulations of the MST‐M(pro) complex crystal structure. The effect of the protonation states of M(pro) H163 residue and MST titratable groups were studied. Furthermore, we identified the MST substituents and M(pro) 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.