In Silico Characterization of Masitinib Interaction with SARS‐CoV‐2 Main Protease. (9th July 2021)

• Record Type: Journal Article
• Authors: Martínez‐Ortega, Ulises; Figueroa‐Figueroa, Diego I.; Hernández‐Luis, Francisco; Aguayo‐Ortiz, Rodrigo
• Is Part Of: ChemMedChem. Volume 16:Number 15(2021)
• Page Start: 2339
• Page End: 2344
• Publication Date: 2021-07-09
• Subjects: SARS-CoV-2 -- Main protease -- Masitinib -- Molecular dynamics -- Protonation states; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100375
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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. Abstract : We performed molecular dynamics simulations to characterize the dynamic behavior of masitinib within the SARS‐CoV‐2 main protease (M pro ) active site. We identified three key interactions involved in complex stability that are altered by the high mobility of the methylpiperazine group. Overall, our results provide essential insights for the design of novel masitinib analogs as potential COVID‐19 drug treatments.