Molecular Docking and Dynamic Simulation Revealed the Potential Inhibitory Activity of Opioid Compounds Targeting the Main Protease of SARS-CoV-2

Abstract

Opioids are a class of chemicals, naturally occurring in the opium poppy plant, and act on the brain to cause a range of impacts, notably analgesic and anti-inflammatory actions. Moreover, an overview was taken in consideration for SARS-CoV-2 incidence and complications, as well as the medicinal uses of opioids were discussed being a safe analgesic and anti-inflammatory drug in a specific dose. Also, our article focused on utilization of opioids in the medication of SARS-CoV-2. Therefore, the major objective of this study was to investigate the antiviral effect of opioids throughout an in silico study by molecular docking study to fifteen opioid compounds against SARS-CoV-2 main protease (PDB ID 6LU7, Mpro). The docking results revealed that opioid complexes potentially inhibit the Mpro active site and exhibiting binding energy (-11.0 kcal/mol), which is comparably higher than the ligand. Furthermore, ADMET prediction indicated that all the tested compounds have good oral absorption and bioavailability and can transport via biological membranes. Finally, Mpro-pholcodine complex was subjected to five MD (RMSD, RMSF, SASA, Rg, and hydrogen bonding) and two MM-PBSA, and conformational change studies, for 100 ns, confirmed the stability of pholcodine, as a representative example, inside the active site of Mpro.