Investigation of The Potential Inhibitor Effects Of Lycorine On Sars-Cov-2 Main Protease (Mpro) Using Molecular Dynamics Simulations and MMPBSA

Authors : Barış Kurt

Pages : 424-435

Doi:10.38001/ijlsb.1110761

View : 12 | Download : 8

Publication Date : 2022-12-15

Article Type : Research

Abstract :The main protease (Mpro or 3CLpro) plays important roles in viral replication and is one of attractive targets for drug development for SARS-CoV-2. In this study, we investigated the potential inhibitory effect of lycorine molecule as a ligand on SARS-CoV-2 using computational approaches. For this purpose, we conducted molecular docking and molecular dynamics simulations MM-PB(GB)SA analyses. The findings showed that the lycorine ligand was successfully docked with catalytic dyad (Cys145 and His41) of SARS-CoV-2 Mpro with binding affinity changing between -6.71 and -7.03 kcal mol-1. MMPB(GB)SA calculations resulted according to GB (Generalized Born) approach in a Gibbs free energy changing between -24.925-+01152 kcal/mol between lycorine and SARS-CoV-2 which is promising. PB (Poisson Boltzmann) approach gave less favorable energy (-2.610±0.2611 kcal mol-1). Thus, Entropy calculations from the normal mode analysis (ΔS) were performed and it supported GB approach and conducted -23.100±6.4635 kcal mol-1. These results showed lycorine has a druggable potential but the drug effect of lycorine on COVID-19 is limited and experimental studies should be done with pharmacokinetic modifications that increase the drug effect of lycorine.
Keywords : Molecular Dynamics Simulation, MMPBSA, Gibbs Energy, SARS-CoV-2