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.