Tags

Type your tag names separated by a space and hit enter

In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease.
ChemMedChem. 2021 08 05; 16(15):2339-2344.C

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

Authors+Show Affiliations

Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34142459

Citation

Martínez-Ortega, Ulises, et al. "In Silico Characterization of Masitinib Interaction With SARS-CoV-2 Main Protease." ChemMedChem, vol. 16, no. 15, 2021, pp. 2339-2344.
Martínez-Ortega U, Figueroa-Figueroa DI, Hernández-Luis F, et al. In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease. ChemMedChem. 2021;16(15):2339-2344.
Martínez-Ortega, U., Figueroa-Figueroa, D. I., Hernández-Luis, F., & Aguayo-Ortiz, R. (2021). In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease. ChemMedChem, 16(15), 2339-2344. https://doi.org/10.1002/cmdc.202100375
Martínez-Ortega U, et al. In Silico Characterization of Masitinib Interaction With SARS-CoV-2 Main Protease. ChemMedChem. 2021 08 5;16(15):2339-2344. PubMed PMID: 34142459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease. AU - Martínez-Ortega,Ulises, AU - Figueroa-Figueroa,Diego I, AU - Hernández-Luis,Francisco, AU - Aguayo-Ortiz,Rodrigo, Y1 - 2021/07/09/ PY - 2021/05/27/received PY - 2021/6/19/pubmed PY - 2021/8/18/medline PY - 2021/6/18/entrez KW - Main protease KW - Masitinib KW - Molecular dynamics KW - Protonation states KW - SARS-CoV-2 SP - 2339 EP - 2344 JF - ChemMedChem JO - ChemMedChem VL - 16 IS - 15 N2 - 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 (Mpro). Although MST is a potential candidate for COVID-19 treatment, a comprehensive analysis of its interaction with Mpro has not been done. In this work, we performed molecular dynamics simulations of the MST-Mpro complex crystal structure. The effect of the protonation states of Mpro H163 residue and MST titratable groups were studied. Furthermore, we identified the MST substituents and Mpro 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. SN - 1860-7187 UR - https://www.unboundmedicine.com/medline/citation/34142459/In_Silico_Characterization_of_Masitinib_Interaction_with_SARS_CoV_2_Main_Protease_ L2 - https://doi.org/10.1002/cmdc.202100375 DB - PRIME DP - Unbound Medicine ER -