Herein, molecular structure of SARS-CoV-2 main protease (Mpro) was used for docking or binding energy analysis with medicinally known anti-HIV protease inhibitor drug molecules at changing pH (4-8). Variance analysis performed on binding energies between pH 4-8 confirmed that the binding energy and mode of interaction of some ligands were variable with pH. Among the selected repurposed protease inhibitors, indinavir and saquinavir showed to have the highest differential binding energy with the changing pH. Using the variance analysis, we also proposed novel structural derivative of saquinavir as a pH sensitive specific protease inhibitor with higher pH related selectivity. Hence, the most pH selective protease inhibitors for treatment of SARS-CoV-2 were identified.
