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

Vatansever, Erol C.; Yang, Kai; Kratch, Kaci C.; Drelich, Aleksandra; Cho, Chia-Chuan; Mellot, Drake M.; Xu, Shiqing; Tseng, Chien-Te K.; Liu, Wenshe Ray

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.