Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered an unprecedented global pandemic in the modern era, infecting millions of people with an approximately 2% death rate. It emerged in late 2019 and researchers worldwide race time to identify druggable targets where medicinal chemists can design potential inhibitors. Objective: Drug repurposing is one of the most convenient methods available now to find already approved drugs for human use with a potential tendency to cure COVID-19. Method: Within this work, the FDA-approved drug database containing 1281 drugs was employed to extract possible drugs that could have activity against the “main protease” enzyme in this virus. Various computer-aided drug design techniques, such as pharmacophore generation, ligand pharmacophore mapping, molecular docking and filtering techniques, were used to identify potential inhibitors. The cocrystallized ligand inside the main protease enzyme was utilized to generate two structure-based pharmacophores that were used as templates for deletion in the FDA database. To validate the selection of the active hits from pharmacophore mapping, molecular docking via “LibDock” was performed, while the highest scoring candidate was selected. Results: Interestingly, three antiviral drugs (lopinavir, saquinavir and remdesivir) were qualified to be potential main protease inhibitors. Conclusion: The researchers in this work recommend clinically investigating the possibility of these drugs as preliminary therapies until selective drugs for COVID-19 virus are approved.