Targeting the SARS-CoV-2 Main Protease to Repurpose Drugs for COVID-19

Guided by a computational docking analysis, about 30 FDA/EMA-approved small molecule medicines were characterized on their inhibition of the SARS-CoV-2 main protease (M ^Pro ). Of these tested small molecule medicines, six displayed an IC ₅₀ value in inhibiting M ^Pro below 100 μM. Three medicines pimozide, ebastine, and bepridil are basic small molecules that are expected to exert a similar effect as hydroxychloroquine in raising endosomal pH for slowing down the SARS-CoV-2 entry into human cell hosts. Bepridil has been previously explored in a high dose as 100 mg/kg for treating diseases. Its high dose use will likely achieve dual functions in treating COVID-19 by both raising the endosomal pH to slow viral entry and inhibiting M ^Pro in infected cells. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.