Pharmacophore Analyses of SARS-CoV-2 Active Main Protease Inhibitors Using Pharmacophore Query and Docking Study

The coronavirus disease (COVID-19) pandemic is the most important current problem in the world. Many researchers have focused on approved drugs or new drug candidates to combat the pandemic. Structural and nonstructural proteins of SARS-CoV-2 have been detected as targets for prevention of host cell infection or blockade of vital function. The main protease that plays an essential role in the virus life cycle is the optimal target. To design new inhibitors against the enzyme, the catalytic active site and substrate-binding site should be well analyzed. In this study, we generated a pharmacophore model using the cocrystallized pose of an active SARS-CoV-2 main protease inhibitor. According to the model, the inhibitor inhibits the enzyme via three hydrogen bond donors, two hydrogen bond acceptors and two aromatic ring interactions. Moreover, we docked reported active inhibitors of the main protease into the catalytic active site and detected matches between their pharmacophore models. The results showed that two close hydrogen acceptor/donor atom pairs and an aromatic ring are essential for enzyme inhibition.