In-silico Screening of Potential Phytochemicals against Extracellular Adherence (Eap) Protein of Staphylococcus aureus from Indian Medicinal Plants

Abstract

Background: Staphylococcus aureus is a threat to human health, it colonizes one-third of the human population via skin or nose and deeper intrusions into tissues have catastrophic consequences. The bacterium secretes virulence proteins like CHIP and SCIN and extracellular adhesins like extracellular adherence (Eap) proteins. Eap and its functionally orphan homologs, EapH1 and EapH2; are a class of secreted proteins that inhibit neutrophil serine proteases such as neutrophil elastase (HNE) that is linked to tissue degradation in a variety of disease conditions including inflammatory disorders. Commercial drugs used against S.aureus such as Nafcillin, Pefloxacin, etc. have been known to have negative effects and are not recommended for children, the elderly, or pregnant women. Objective: The current research focuses on discovering phytochemicals found in Indian medicinal herbs that have been used as spices for ages and are already beneficial against a variety of illnesses and ailments to be used against Eap proteins. Method: Molecular docking;absorption, distribution, metabolism, excretion, toxicity (ADMET) analysis and Simulation were performed to see if these phytochemicals interact with the active site residues of Eap proteins and function as competitive inhibitors of NE and to know their drug like properties and gather information about the system dynamics. 19 phytochemicals were selected from receptor-ligand docking. The selected molecules were pharmacologically tested through Lipinski’s analysis; to know their ability for being formulated into drugs. ADMET analysis was carried out to define the biological characteristic of phytochemicals inside the living body. The phytochemicals with the best docking score and drug likeliness were analysed by Molecular Simulation to observe the fluctuation of participating and interacting amino acids with Eaph1 and Eaph2 respectively. Result: Among the nineteen phytochemicals that were chosen for docking only the best eleven interactions were chosen for ADMET analysis. The top hit phytochemicals for Eaph1 and Eaph2 were Curcumin and Eugenol respectively, which was well demonstrated by Molecular dynamic simulation. Conclusion: The present study has established the hypothesis that phytochemicals have a scope to replace commercial drugs against the Eap virulence system of Staphylococcus aureus