The anticoagulant potential of Lippia Alba extract in inhibiting SARS-CoV-2 Mpro: Density functional calculation, molecular docking analysis, and molecular dynamics simulations

Abstract

Lippia Alba, a plant commonly utilized in traditional folk medicine, particularly in Brazil, is renowned for its essential oil possessing anti-inflammatory, antibacterial, anesthetic, and antiviral properties. In this study, we conducted molecular analysis, density function calculations, and molecular dynamics simulations to evaluate 13 novel anticoagulant compounds derived from the chemical composition of Lippia Alba, with potential anti-SARS-CoV-2 activity. Our investigation focused on the SARS-CoV-2-associated protein, PDB ID: 6Y2G. Comparative analysis with the reference drug Calpain Inhibitor II revealed that all compounds exhibited a high binding affinity to the SARS-CoV-2 Mpro protein, ranging from -7,5 to -9,9 kcal/mol. Among them, three compounds (C10, C12, and C13) demonstrated favorable pharmacokinetic properties, complying with Lipinski's rule of five. Additionally, Density Functional Theory (DFT) calculations were performed to determine quantum parameters, and a 100ns molecular dynamics simulation provided insights into the binding stability of the promising compounds within the target protein pocket. Based on our findings, compound 10 shows potential as an effective drug molecule for inhibiting SARS-CoV-2.