Computational screening of camostat and related compounds against human TMPRSS2: A potential treatment of COVID-19.

ABSTRACT

The global coronavirus pandemic has burdened the human population with mass fatalities and disastrous socio-economic consequences. The frequent occurrence of these new variants has fueled the already prevailing challenge. There is still a necessity for highly effective small molecular agents to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we targeted the human transmembrane surface protease TMPRSS2, which is essential for proteolytic activation of SARS-CoV-2. Camostat is a well-known inhibitor of serine proteases and an effective TMPRSS2 inhibitor. A virtual library of camostat-like compounds was computationally screened against the catalytic site of TMPRSS2. Following a sequential in-depth molecular docking and dynamics simulation, we report the compounds that exhibited promising efficacy against TMPRSS2. The molecular docking and MM/PBSA free energy calculation study indicates these compounds carry excellent binding affinity against TMPRSS2 and found them more effective than camostat. The study will open doors for the effective treatment of coronavirus disease 2019.