Multi-targeted molecular docking, pharmacokinetics, and drug-likeness evaluation of coumarin based compounds targeting proteins involved in development of COVID-19

Abstract

COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of deaths every single day. The present research was aimed to study the multi-target interaction of coumarins against COVID-19 using molecular docking analysis. The structure of coumarin compounds was checked for ADME and Lipinski rule of five by using SwissADME, an online tool. SARS-CoV-2 proteins such as RdRp, PLpro, Mpro and spike protein were collected from the Protein Data Bank. The molecular docking study was performed in the PyRx tool, and the molecular interactions were visualised by Discovery Studio Visualizer. All the coumarin compounds used in the study were obeyed Lipinski’s rule of 5 without any violations. All the three designed derivatives of phenprocoumon, hymecromone, and psoralen were showed high binding affinity and prominent interactions with the drug target. The presence of –OH groups in the compound, His41, a catalytic dyad in Mpro, number of and the distance of hydrogen bond interactions with SARS-CoV-2 targets was accountable for the high binding attractions. The modified drug structures possess better binding efficacy towards at least three targets compared to their parent compounds. Further, molecular dynamic studies can be suggested to find the ligand–protein complex stability. The present study outcome reveals that the designed coumarins can be synthesised and examined as a potent inhibitory drug of SARS-CoV-2.