DFT, molecular docking and molecular dynamics simulation studies on natural chromone derivatives from Cassia nomame for their possible antiviral activity against Coronavirus, SARS-CoV-2

In this study, two naturally occurred chromone derivatives obtained from Cassia nomame which are recently entered the literature, have been investigated computationally for their potential antiviral activity against SARS-CoV-2. In the first part of the study, DFT calculations were performed on the investigated compounds. In this part, geometry optimizations, frequency analyses, molecular electrostatic potential map calculations, frontier molecular orbital calculations and NMR spectral studies have been performed. In the second part of the study, molecular docking calculations were performed. SARS-CoV-2 main protease (SARS-CoV-2 Mpro) was selected as receptor for molecular docking calculations. In the third part of the study, molecular dynamics simulation studies were performed on the top scoring SARS-CoV-2 Mpro – ligand complexes. In this part, binding free energy calculations were also performed on the SARS-CoV-2 Mpro – ligand complexes with the use of molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method. Results showed that, two naturally occurred chromone derivatives, 5-(isobutyryl)-2-(2-oxopropyl)-7-methoxy-4H-chromen-4-one and 5-(isobutyryl)-2-(2-oxopropyl)-6-methoxy-4H-chromen-4-one, showed quite high binding affinity to SARS-CoV-2 Mpro and remained stable during the molecular dynamics simulations. Additionally, in the last part of the study, drug-likeness analyses were performed on the investigated compounds with the use of Lipinski's rule of five and no violation was observed.