In silico Identification of Antiviral Polyphenols from Phoenix dactylifera Targeting SARS-CoV-2 Main Protease

Abstract

COVID-19, caused by SARS-CoV-2, depends on its main protease (Mpro) for viral replication. This study evaluated the potential of polyphenolic compounds from Phoenix dactylifera as Mpro inhibitors using molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Three ligands - flavoxanthin, violaxanthin, and neoxanthin, demonstrated the strongest binding affinities to Mpro, although still lower than tipranavir. MD simulations indicated that all three ligands maintained stable interactions with Mpro, while PCA revealed no major structural deviations in the complex. ADMET screening identified 18 compounds with acceptable pharmacokinetic properties. Overall, the top three ligands exhibited favorable binding energies and stability, supporting their potential as Mpro inhibitors. Further in vitro and in vivo validation is needed to support this hypothesis.