Strong binding of Leupeptin with TMPRSS2 protease may be an alternate to
Camostat and Nafamostat for SARS-CoV-2 repurposed drug: Proof from
Molecular docking and Molecular dynamics simulations
Abstract
The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China caused
acute respiratory infection to humans. There is no precise
vaccine/therapeutic agents available to combat the COVID-19 disease.
Some repurposed drugs are saving the life of diseased, but the complete
cure is relatively less. Several drug targets have been reported to
inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (Transmembrane
protease serine 2) is one of the potential targets, inhibiting this
protease stops the virus entry into the host human cell. Camostat
mesylate, nafamostat and leupeptin are the drugs, in which the first two
drugs are being used for COVID-19 and leupeptin also tested. To consider
these as repurposed drugs for COVID-19, it is essential to understand
their binding affinity and stability with TMPRSS2. In the present study,
we performed the molecular docking and molecular dynamics (MD)
simulation for the three molecules with the TMPRSS2. The docking study
reveals that leupeptin molecule strongly binds with TMPRSS2 protein than
the other two drug molecules. The RMSD and RMSF values of MD simulations
shows, leupeptin and the amino acids of TMPRSS2 are very stable than the
other molecules. Furthermore, leupeptin forms interactions with the key
amino acids of TMPRSS2 and the same have been maintained during the MD
simulations. This structural and dynamical information is useful to
evaluate these drugs to be used as repurposed drugs, however, the strong
binding profile of leupeptin with TMPRSS2, suggests, it may be
considered as a repurposed drug for COVID-19 after clinical trial.