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Article: Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system

TitleDiscovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system
Authors
KeywordsAntiviral
Coronavirus
COVID-19
Library
SARS-CoV-2
Issue Date2020
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618
Citation
Pharmacological Research, 2020, v. 159, p. 104960 How to Cite?
AbstractCoronavirus 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 (EC50) 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 (EC50 1.13–2.01 μM). Bexarotene demonstrated the highest Cmax:EC50 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.
Persistent Identifierhttp://hdl.handle.net/10722/287586
ISSN
2019 Impact Factor: 5.893
2015 SCImago Journal Rankings: 2.108
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorChan, JFW-
dc.contributor.authorChik, KKH-
dc.contributor.authorChan, CCY-
dc.contributor.authorTsang, JOL-
dc.contributor.authorLiang, R-
dc.contributor.authorCao, J-
dc.contributor.authorTang, K-
dc.contributor.authorChen, LL-
dc.contributor.authorWen, K-
dc.contributor.authorCai, JP-
dc.contributor.authorYe, ZW-
dc.contributor.authorLu, G-
dc.contributor.authorChu, H-
dc.contributor.authorJin, DY-
dc.contributor.authorYuen, KY-
dc.date.accessioned2020-10-05T12:00:14Z-
dc.date.available2020-10-05T12:00:14Z-
dc.date.issued2020-
dc.identifier.citationPharmacological Research, 2020, v. 159, p. 104960-
dc.identifier.issn1043-6618-
dc.identifier.urihttp://hdl.handle.net/10722/287586-
dc.description.abstractCoronavirus 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 (EC50) 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 (EC50 1.13–2.01 μM). Bexarotene demonstrated the highest Cmax:EC50 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.-
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618-
dc.relation.ispartofPharmacological Research-
dc.subjectAntiviral-
dc.subjectCoronavirus-
dc.subjectCOVID-19-
dc.subjectLibrary-
dc.subjectSARS-CoV-2-
dc.titleDiscovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system-
dc.typeArticle-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailTsang, JOL: oltsang@HKUCC-COM.hku.hk-
dc.identifier.emailLiang, R: liangrh@HKUCC-COM.hku.hk-
dc.identifier.emailTang, K: kmtang20@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailYe, ZW: zwye@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.phrs.2020.104960-
dc.identifier.pmid32473310-
dc.identifier.pmcidPMC7254006-
dc.identifier.scopuseid_2-s2.0-85085770987-
dc.identifier.hkuros315476-
dc.identifier.volume159-
dc.identifier.spage104960-
dc.identifier.epage104960-
dc.publisher.placeUnited Kingdom-

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