In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease
Por:
Martinez-Ortega, Ulises, Figueroa-Figueroa, I, Diego, Hernandez-Luis, Francisco, Aguayo-Ortiz, Rodrigo
Publicada:
5 ago 2021
Ahead of Print:
1 jul 2021
Resumen:
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.
Filiaciones:
Martinez-Ortega, Ulises:
Aguayo-Ortiz, R (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico. Martinez-Ortega, Ulises
Figueroa-Figueroa, I, Diego:
Aguayo-Ortiz, R (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico. Martinez-Ortega, Ulises
Hernandez-Luis, Francisco:
Aguayo-Ortiz, R (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico. Martinez-Ortega, Ulises
Aguayo-Ortiz, Rodrigo:
Aguayo-Ortiz, R (Corresponding Author), Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico. Martinez-Ortega, Ulises
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