Armaghane Danesh Bimonthly Journal (Jul 2024)
Molecular Docking of Thymus Vulgaris Biochemical Against Candida Albicans Secreted Aspartyl Protease 5 to Find Possible Inhibitory Compounds
Abstract
Background & aim: Despite being considered a common yeast among humans, Candida albicans can become an invasive agent under certain conditions and cause various types of acute or chronic infections. The use of existing antifungal drugs is limited due to their side effects and the resistance of this yeast to them. Previous in vitro studies have demonstrated that thyme plant possesses antifungal properties and its metabolites have the ability to kill the candida strains resistant to azole antifungal drugs. Secreted aspartyl protease 5 (SAP5) plays a crucial role in the pathogenicity of this yeast. Therefore, the aim of the present study was to determine and investigate the molecular docking of biological compounds of garden thyme (L. Thymus vulgaris) with secreted aspartyl protease-5 of Candida albicans yeast to find possible inhibitory compounds. Methods: In the present molecular docking study conducted in 2024, the active phytochemical compounds of the Thymus vulgaris plant were obtained from the LOTUS and NPASS databases. The structure of the SAP5 protein was retrieved from the RCSB PDB database. Molecular docking of ligands with the SAP5 enzyme was performed using AutoDock Vina in the PyRx 0.8 software package to calculate binding energies and determine the docking position of each compound in its interaction with SAP5. The compounds with the best binding energy to the target protein were further evaluated for pharmacokinetic properties and toxicity, and the selected ligands were visualized using BIOVIA Discovery Studio. The collected data were analyzed using different software and compared with the results of previous articles in this field. Results: The binding energies of Thymus vulgaris compounds to the active site of the SAP5 enzyme ranged from -9.9 to -3.4 kcal/mol. The highest binding affinities to the active site were observed for the compounds Eriodictin, (-)-Taxifolin, and Ellagic Acid. These compounds also demonstrated favorable pharmacokinetic and toxicity profiles. Pharmacokinetic studies of three selected compounds using the SwissADME online server showed their promising medicinal properties. Despite this, investigating their toxicity using ADMETlab and ProTox-II servers showed the toxicity of eriodictin. Conclusion: The results of the present study indicated that some compounds in thyme plant may inhibit SAP5. Therefore, probably one of the mechanisms involved in the anti-candidal effects of garden thyme on Candida albicans yeast is through the inhibition of this protein.
