Molecular Docking and Pharmacokinetic Studies of Aquillochin and Grewin as SARS-CoV-2 Mpro Inhibitors

Abstract

Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 dis-ease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study. Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were de-termined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand effi-ciency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison. Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were iden-tified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be -7.5 and -8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharma-cokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were conso-nant with the many accepted rules and the criteria of drug-likeness. Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease.