期刊
PHARMACOLOGICAL RESEARCH
卷 159, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2020.104960
关键词
Antiviral; Coronavirus; COVID-19; Library; SARS-CoV-2; Treatment; Cetilistat; Diiodohydroxyquinoline; Abiraterone; Bexarotene
资金
- Health@InnoHK (Centre for Virology, Vaccinology and Therapeutics), Innovation and Technology Commission, The Government of the Hong Kong Special Administrative Region of the People's Republic of China
- National Program on Key Research Project of China [2020YFA0707500, 2020YFA0707504]
- Research Grants Council, Hong Kong Special Administrative Region [T11/707/15]
- High Level-Hospital Program, Health Commission of Guangdong Province, China
- Shaw Foundation of Hong Kong
- Respiratory Viral Research Foundation Limited
- Chow Sin Lan Charity Fund Limited
- Chan Yin Chuen Memorial Charitable Foundation
- Hong Kong Hainan Commercial Association South China Microbiology Research Fund
- Jessie AMP
- George Ho Charitable Foundation
- Perfect Shape Medical Limited
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 (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 antiSARS-CoV-2 activity (EC50 1.13-2.01 mu M). 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.
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