Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids: in silico approach

Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids

Abstract

Background

The scientific researches on COVID-19 pandemic topics are headed to an explosion of scientific literature. Despite these global efforts, the efficient treatment of patients is an in-progress challenge.  Based on a meta-study of published evidences about the compounds and their botanic sources in the last six decades, we have identified two potential flavonoids with high binding capacity and possible drug candidates against Mpro.

Methods

 AUTODOCK tools 1.5.6.LigPlot+  and Protein-ligand Interaction Profiler was used to visualize the binding interactions. ADMET and drug-likeness study of ligands was done using OSIRIS Property Explorer and admetSAR.  MD simulation was performed to check the stability of the ligand-enzyme complexes using UNRES web server.

Results

14 Flavonoids having antiviral properties and 4 existing drugs were used as ligands to bind to the COVID-19 main protease. Out of these ligands, flavonoids procyanidin b2 and mangiferin showed high binding affinity with the Mpro having Docking affinity of -9.4 and -8.5kcal/mol respectively.

Conclusion

Our results propose that flavonoids such as Procyanidin b2 and mangiferin have a better binding affinity to Mpro of COVID-19 than hydroxyhloroquine, favipiravir and remdesivir. These compounds with good binding potency support the potential as starting points for therapeutics against COVID-19.