IDENTIFICATION OF NOVEL COUMARIN BASED COMPOUNDS AS POTENTIAL INHIBITORS OF THE 3-CHYMOTRYPSIN-LIKE MAIN PROTEASE OF SARS-COV-2 USING DFT, MOLECULAR DOCKING AND MOLECULAR DYNAMICS SIMULATION STUDIES
G. Salgado-Moran, Wilson Cardona V., Lorena Gerli Candia, L.H. Mendoza-Huizar, Tooba Abdizadeh · Journal of the Chilean Chemical Society · 2022
SARS-CoV-2 is the pandemic disease-causing agent COVID-19 with high infection rates.Despite the progress made in vaccine development, there is an urgent need for the identification of antiviral compounds that can tackle better the different phases of SARS-CoV-2.The main protease (Mpro or 3CLpro) of SARS-CoV-2 has a crucial role in viral replication and transcription.In this study, an in silico method was executed to elucidate the inhibitory potential of the synthesized 6-tert-octyl and 6-8-ditert-butyl coumarin compounds against the major protease of SARS-CoV-2 by comprehensive molecular docking and density functional theory (DFT), ADMET properties and molecular dynamics simulation approaches.Both compounds shown favorable interactions with the 3CLpro of the virus.From DFT calculations, HOMO-LUMO values and global descriptors indicated promising results for these compounds.Furthermore, molecular dynamics studies revealed that these ligand-receptor complexes remain stable during simulations and both compounds showed considerably high binding affinity to the main SARS-CoV-2 protease.The results of the study suggest that the coumarin compounds 6-tert-octyl and 6-8-ditert-butyl could be considered as promising scaffolds for the development of potential COVID-19 inhibitors after further studies.