Investigating the Interaction of Herbal Medicinal Compounds Against Mpro Protease in SARS-CoV-2 Virus Strains

Introduction: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. The identification of beneficial plant compounds and their use for targeting important proteins involved in the infection and replication of the coronavirus is considered an effective option in the fight against this disease. The aim of this research was to investigate the interaction of native medicinal plant compounds against the Mpro protease of different SARS-CoV-2 strains and to determine and evaluate the final compound using the HPLC method. Methods: The three-dimensional structure of the Mpro protease was obtained from the PDB database. Various antiviral plant compounds were collected from databases and articles. Molecular docking was performed using AutoDock Vina. The features and properties of the selected compounds were examined using different servers. Mutagenesis for the methionine amino acid 49 was performed, and a new three-dimensional structure of the Mpro protein was modeled for different virus strains. Docking analysis for four selected compounds was conducted based on binding energy. Molecular dynamics simulation (MD) was carried out to examine the stability of the final structure, and HPLC was used to evaluate the presence of the effective compound in the desired plant. Results: Docking results showed that the compound Cyanidin-3, 5-di-o-glucoside is effective in inhibiting Mpro, as indicated by its favorable total binding energy. The pharmacokinetic properties of this compound were also determined. MD results indicated that the Mpro-Cyanidin-3, 5-di-o-glucoside complex is stable. HPLC confirmed the presence of Cyanidin-3, 5-di-o-glucoside in Iranian pomegranate extract. Conclusion: The compound Cyanidin-3, 5-di-o-glucoside found in Iranian pomegranate extract can bind to Mpro with high affinity and inhibit its activity, potentially serving as a drug that directly targets the coronavirus.