tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Mar 9;118(10):e2012201118.
doi: 10.1073/pnas.2012201118.
Bepridil is potent against SARS-CoV-2 in vitro
Erol C Vatansever[SUP] 1 [/SUP], Kai S Yang[SUP] 1 [/SUP], Aleksandra K Drelich[SUP] 2 [/SUP], Kaci C Kratch[SUP] 1 [/SUP], Chia-Chuan Cho[SUP] 1 [/SUP], Kempaiah Rayavara Kempaiah[SUP] 2 [/SUP], Jason C Hsu[SUP] 2 [/SUP], Drake M Mellott[SUP] 3 [/SUP], Shiqing Xu[SUP] 1 [/SUP], Chien-Te K Tseng[SUP] 4 5 [/SUP], Wenshe Ray Liu[SUP] 6 3 7 8 9 [/SUP]
Affiliations
Abstract
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[SUP]p[/SUP][SUP]ro[/SUP]). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC[SUB]50[/SUB]) value below 100 μM in inhibiting M[SUP]p[/SUP][SUP]ro[/SUP], 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[SUP]p[/SUP][SUP]ro[/SUP] 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[SUB]50[/SUB]) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.
Keywords: COVID-19; SARS-CoV-2; bepridil; drug repurposing; main protease.
. 2021 Mar 9;118(10):e2012201118.
doi: 10.1073/pnas.2012201118.
Bepridil is potent against SARS-CoV-2 in vitro
Erol C Vatansever[SUP] 1 [/SUP], Kai S Yang[SUP] 1 [/SUP], Aleksandra K Drelich[SUP] 2 [/SUP], Kaci C Kratch[SUP] 1 [/SUP], Chia-Chuan Cho[SUP] 1 [/SUP], Kempaiah Rayavara Kempaiah[SUP] 2 [/SUP], Jason C Hsu[SUP] 2 [/SUP], Drake M Mellott[SUP] 3 [/SUP], Shiqing Xu[SUP] 1 [/SUP], Chien-Te K Tseng[SUP] 4 5 [/SUP], Wenshe Ray Liu[SUP] 6 3 7 8 9 [/SUP]
Affiliations
- PMID: 33597253
- DOI: 10.1073/pnas.2012201118
Abstract
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[SUP]p[/SUP][SUP]ro[/SUP]). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC[SUB]50[/SUB]) value below 100 μM in inhibiting M[SUP]p[/SUP][SUP]ro[/SUP], 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[SUP]p[/SUP][SUP]ro[/SUP] 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[SUB]50[/SUB]) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.
Keywords: COVID-19; SARS-CoV-2; bepridil; drug repurposing; main protease.