RETRACTED: A Drug Repurposing Approach to Identify Therapeutics by Screening Medicines for Malaria Ventures Exploiting SARS-CoV-2 Main Protease

COVID-19 pandemic makes the human-kind standstill and results in high morbidity and mortality cases worldwide. Still, there are no approved antiviral drugs with proven efficacy nor any therapeutic vaccines to combat the disease as per the current date. In the present study, SARS-CoV-2 main protease (Mpro) has been taken as a potential drug target considering its crucial role in virus propagation. We have used 400 diverse bioactive inhibitors with proven antibacterial and antiviral properties for screening against Mpro target. Our screening result identifies ten compounds with higher binding affinity than N3 (used as a reference compound to validate the experiment). All the compounds possess desire physicochemical properties. Later on, in-depth docking and superimposition of selected complexes confirm that only three compounds (MMV1782211, MMV1782220 and MMV1578574) are actively interacting with the catalytic domain of Mpro.

Furthermore, the selected three molecules complexed with Mpro and N3-Mpro as control are subjected to molecular dynamics simulation study (root means square deviation, root mean square fluctuation, hydrogen bonding, solvent-accessible area and radius of gyration). MMV1782211-Mpro complex shows a strong and stable interaction as compared to others. The MM/PBSA free energy calculation shows the highest binding free energy of –115.8 kJ/mol for MMV1782211 compound also cross-confirms our molecular docking study. Therefore, our in silico findings become very interesting towards developing alternative medicine against SARS-CoV-2 Mpro target. So, we can expect prompt actions in this direction to combat the COVID-19.