tetano
Editor, Senior Moderator
Pharmacol Res
. 2020 May 27;104960.
doi: 10.1016/j.phrs.2020.104960. Online ahead of print.
Discovery of the FDA-approved Drugs Bexarotene, Cetilistat, Diiodohydroxyquinoline, and Abiraterone as Potential COVID-19 Treatments With a Robust Two-Tier Screening System
Shuofeng Yuan[SUP] 1 [/SUP], Jasper F W Chan[SUP] 2 [/SUP], Kenn K H Chik[SUP] 1 [/SUP], Chris C Y Chan[SUP] 1 [/SUP], Jessica O L Tsang[SUP] 1 [/SUP], Ronghui Liang[SUP] 1 [/SUP], Jianli Cao[SUP] 1 [/SUP], Kaiming Tang[SUP] 1 [/SUP], Lin-Lei Chen[SUP] 1 [/SUP], Kun Wen[SUP] 3 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 1 [/SUP], Gang Lu[SUP] 4 [/SUP], Hin Chu[SUP] 1 [/SUP], Dong-Yan Jin[SUP] 5 [/SUP], Kwok-Yung Yuen[SUP] 6 [/SUP]
Affiliations
Abstract
Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10% depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50% maximal effective concentrations (EC[SUB]50[/SUB]) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC[SUB]50[/SUB] 1.13-2.01?M). Bexarotene demonstrated the highest Cmax:EC[SUB]50[/SUB] ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.
Keywords: Abiraterone acetate (PubChem CID: 9821849); Bexarotene (PubChem CID: 82146); COVID-19; Cetilistat (PubChem CID: 9952916); Diiodohydroxyquinoline (PubChem CID: 3728); SARS-CoV-2; abiraterone; antiviral; bexarotene; cetilistat; coronavirus; diiodohydroxyquinoline; library; treatment.
. 2020 May 27;104960.
doi: 10.1016/j.phrs.2020.104960. Online ahead of print.
Discovery of the FDA-approved Drugs Bexarotene, Cetilistat, Diiodohydroxyquinoline, and Abiraterone as Potential COVID-19 Treatments With a Robust Two-Tier Screening System
Shuofeng Yuan[SUP] 1 [/SUP], Jasper F W Chan[SUP] 2 [/SUP], Kenn K H Chik[SUP] 1 [/SUP], Chris C Y Chan[SUP] 1 [/SUP], Jessica O L Tsang[SUP] 1 [/SUP], Ronghui Liang[SUP] 1 [/SUP], Jianli Cao[SUP] 1 [/SUP], Kaiming Tang[SUP] 1 [/SUP], Lin-Lei Chen[SUP] 1 [/SUP], Kun Wen[SUP] 3 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 1 [/SUP], Gang Lu[SUP] 4 [/SUP], Hin Chu[SUP] 1 [/SUP], Dong-Yan Jin[SUP] 5 [/SUP], Kwok-Yung Yuen[SUP] 6 [/SUP]
Affiliations
- PMID: 32473310
- DOI: 10.1016/j.phrs.2020.104960
Abstract
Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10% depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50% maximal effective concentrations (EC[SUB]50[/SUB]) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC[SUB]50[/SUB] 1.13-2.01?M). Bexarotene demonstrated the highest Cmax:EC[SUB]50[/SUB] ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.
Keywords: Abiraterone acetate (PubChem CID: 9821849); Bexarotene (PubChem CID: 82146); COVID-19; Cetilistat (PubChem CID: 9952916); Diiodohydroxyquinoline (PubChem CID: 3728); SARS-CoV-2; abiraterone; antiviral; bexarotene; cetilistat; coronavirus; diiodohydroxyquinoline; library; treatment.