Conclusions
To meet out the urgent need of drugs to treat the COVID-19 pandemic disease, repurposing drugs is the only feasible solution. In the line of drug searching process, we have undertaken camostat, nafamostat and leupeptin drug molecules to inhibit the TMPRSS2 serine 2 protease, which is the activator of SARS-CoV-2 for the fusion of the virus enter the host human cell. The molecular docking study reveals that these three drug molecules form interactions and has binding affinity towards TMPRSS2. However, the leupeptin forms strong interactions with the key amino acids Ser186, His41, and Asp180 of catalytic triad present in the active site of TMPRSS2 as the other two molecules lacking Ser186 and His41 interactions. Whereas in the molecular dynamics simulations of these three complexes, leupeptin is highly stable (RMSD & RMSF) and this molecule also forms stable interactions with the key amino acids Ser186, His41, and Asp186 of TMPRSS2 during the 100 ns MD simulations. On compare the binding free energy of all the three molecules, notably, leupeptin has high binding affinity towards TMPRSS2. From the static and dynamic studies, it is confirmed that leupeptin is very stable and it could strongly inhibit the TRMPRSS2 serine 2 protease and this leads to stop the fusion of SARS-CoV-2 virus into the host human cell, hence it may be consider as a repurposed drug after clinical studies.