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In Silico Characterization of Masitinib Interaction with SARS‐CoV‐2 Main Protease
Author(s) -
MartínezOrtega Ulises,
FigueroaFigueroa Diego I.,
HernándezLuis Francisco,
AguayoOrtiz Rodrigo
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100375
Subject(s) - protease , in silico , protease inhibitor (pharmacology) , coronavirus , covid-19 , computational biology , virology , chemistry , biology , medicine , virus , biochemistry , enzyme , gene , disease , infectious disease (medical specialty) , viral load , antiretroviral therapy
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.