Computational study of the molecular interactions between thymol and the HIS41 and CYS145 residues present in the active site of the 3CLpro protease

• Main Authors: González Acosta, José Gregorio, Parra, José Gregorio, Iza, Peter
• Format: Article in Journal/Newspaper
• Language: Spanish
• Published: Universidad Nacional de Colombia - Sede Bogotá - Facultad de Ciencias - Departamento de Química 2024
• Subjects: Molecular docking; hydrogen bonding; protease 3CL; residues; thymol; Computational Chemistry; Acoplamiento molecular; enlace de hidrógeno; proteasa 3CL; residuos de aminoacidos; timol; Fisicoquímica; Docking molecular; ligação de hidrogênio; protease; resíduos; Cuantica Química; Orca
• Online Access: https://revistas.unal.edu.co/index.php/rcolquim/article/view/110606

The protease 3CLpro of the SARS-CoV-2 is a crucial enzyme for viral replication, becoming a highly important therapeutic target. Thymol (2-isopropyl-5-methylphenol), a naturally occurring compound found in thyme, exhibits potential antiviral activity against the 3CLpro protease. In this study, using molecular docking with AutoDockTools-1.5.6, the molecular interaction energies between thymol and amino acid residues in the active site of the protein protease 3CLpro were evaluated. Then, with the Atoms in Molecules (QTAIM) and Non-covalent Interactions (NCI) theories, the types of molecular interactions between identified amino acid residues and thymol were analyzed. Quantum calculations were carried out with the Orca-5.0.3 software using the DFT method with the M06-2X functional and the aug-cc-pVDZ basis set in the gas phase. The molecular docking results indicate that thymol is linked to the 3CL protein with an interaction energy equal to -3.784 kcal/mol. QTAIM analysis indicates the presence of critical binding sites between thymol and residues HIS41 and CYS145. In addition, the formation of a hydrogen bond between the OH group of thymol and the CYS145 residue is observed, which is corroborated by the ELF and NCI analyses. Finally, the NCI method confirms the presence of van der Waals interactions with the HIS41 residue. The results suggest that the mechanism of inhibition of the activity of the 3CLpro protein is controlled by molecular interactions such as hydrogen bonding and weak interactions. La proteína proteasa 3CLpro del SARS-CoV-2 es una enzima crucial para la replicación viral, convirtiéndose en un blanco terapéutico de gran importancia. El timol (2-isopropil-5-metilfenol), un compuesto natural que se encuentra en el tomillo (Thymus vulgaris), exhibe potencial actividad antiviral contra la proteasa 3CLpro. En este estudio, usando acoplamiento molecular con AutoDockTools-1.5.6, se evaluaron las energías de interacción molecular entre el timol y los residuos de aminoácidos en el sitio activo de la ...