Molecular Docking of Novel 5-O-benzoylpinostrobin Derivatives as SARS-CoV-2 Main Protease Inhibitors

Background: COVID-19, a global pandemic caused by SARS-CoV-2 infection, has led researchers around the world to search for therapeutic agents for treatment of the disease. The main protease (MPro) of SARS-CoV-2 is one of the potential targets in the development of new drug compounds for the disease. Some known drugs such as chloroquine and remdesivir have been repurposed for treatment of COVID-19, although the the mechanism of action of these compounds is still unknown. In addition to these known drugs, new drug compounds such as 5-O-benzoylpinostrobin derivatives are also potentially used as SARS-CoV-2 MPro inhibitors. This study aims to determine the potential of 5-O-benzoylpinostrobin derivatives as SARSCoV-2 MPro inhibitors, compared with several other compounds used in COVID-19 therapy.
Methods: In silico study was carried out by molecular docking of 5-O-benzoylpinostrobin derivatives using Autodock Vina on two SARS-CoV-2 MPro receptors with PDB IDs of 5R84 and 6LU7. The free energy of binding was calculated and the the interactions of each ligand were analyzed and compared with reference ligand.
Results: Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystalized ligands. These three compounds even exhibited promising results in comparison with other reference ligands such as remdesivir and indinavir.
Conclusion: The results of this investigation anticipate that some 5-O-benzoylpinostrobin derivatives have the potential as SARS-CoV-2 MPro inhibitors.