期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：10
页码：1
DOI：10.1073/pnas.2012201118
出版社：The National Academy of Sciences of the United States of America
摘要：Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M p ro ). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC 50 ) value below 100 μM in inhibiting M p ro , and, importantly, three, that is, pimozide, ebastine, and bepridil, are basic molecules that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting M p ro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti−SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC 50 ) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.
关键词：COVID-19 ; SARS-CoV-2 ; main protease ; bepridil ; drug repurposing
