Molecular Docking and Dynamic Simulation Revealed the Potential Inhibitory Activity of Opioid Compounds Targeting the Main Protease of SARS‐CoV‐2
Samaher S. A. Mahmoud, Eslam B. Elkaeed, Aisha A. Alsfouk, Elshimaa M. N. Abdelhafez · BioMed Research International · 2022
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.