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10.1016/j.phrs.2020.104960

http://scihub22266oqcxt.onion/10.1016/j.phrs.2020.104960
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suck abstract from ncbi


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pmid32473310      Pharmacol+Res 2020 ; 159 (ä): 104960
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  • Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system #MMPMID32473310
  • Yuan S; Chan JFW; Chik KKH; Chan CCY; Tsang JOL; Liang R; Cao J; Tang K; Chen LL; Wen K; Cai JP; Ye ZW; Lu G; Chu H; Jin DY; Yuen KY
  • Pharmacol Res 2020[Sep]; 159 (ä): 104960 PMID32473310show ga
  • 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(50)) 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(50) 1.13-2.01 muM). Bexarotene demonstrated the highest Cmax:EC(50) 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.
  • |*Betacoronavirus/drug effects/physiology[MESH]
  • |Androstenes/pharmacology[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Benzoxazines/pharmacology[MESH]
  • |Bexarotene/pharmacology[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Caco-2 Cells[MESH]
  • |Cell Survival/drug effects[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus Infections/*drug therapy/virology[MESH]
  • |Cytopathogenic Effect, Viral/drug effects[MESH]
  • |Databases, Pharmaceutical[MESH]
  • |Drug Approval[MESH]
  • |Drug Evaluation, Preclinical/*methods[MESH]
  • |Drug Repositioning[MESH]
  • |Enzyme-Linked Immunosorbent Assay[MESH]
  • |Humans[MESH]
  • |Iodoquinol/pharmacology[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy/virology[MESH]
  • |SARS-CoV-2[MESH]
  • |United States[MESH]
  • |United States Food and Drug Administration[MESH]
  • |Vero Cells[MESH]
  • |Viral Load/drug effects[MESH]


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