Molecular docking, simulation and ADMET studies of phenolic compounds from olive oil against main protease and RNA-dependent RNA polymerase of SARS-CoV-2.

Plant extracts exhibit notable anti-SARS-CoV-2 potential due to their richness in biologically active phenolic compounds. This study aimed to evaluate the inhibitory activity of phenolic constituents from Morocco Picholine virgin olive oil (VOO) against two key SARS-CoV-2 enzymes: the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). A total of 18 phenolic compounds were screened and docked with both targets using iGEMDOCK and MGL Tools. Molecular dynamics simulations and in silico ADMET analyses were subsequently conducted to assess the stability and drug-likeness of the ligand-protein complexes. Oleuropein aglycone, elenolic acid, hydroxytyrosol, and tyrosol exhibited the strongest binding affinity towards Mpro, whereas oleuropein aglycone, oleocanthal, and hydroxytyrosol demonstrated the highest affinity for RdRp. These findings suggest that Mpro and RdRp are promising therapeutic targets and the selected VOO phenolic compounds may serve as potential inhibitors for the development of anti-SARS-CoV-2 agents.