2. Academic Validation
  3. Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system

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

  • Pharmacol Res. 2020 Sep;159:104960. doi: 10.1016/j.phrs.2020.104960.
Shuofeng Yuan 1,  Jasper F W Chan 2,  Kenn K H Chik 1,  Chris C Y Chan 1,  Jessica O L Tsang 1,  Ronghui Liang 1,  Jianli Cao 1,  Kaiming Tang 1,  Lin-Lei Chen 1,  Kun Wen 3,  Jian-Piao Cai 1,  Zi-Wei Ye 1,  Gang Lu 4,  Hin Chu 1,  Dong-Yan Jin 5,  Kwok-Yung Yuen 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region.
  • 2 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region. Electronic address: jfwchan@hku.hk.
  • 3 Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 4 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Department of Pathogen Biology, Hainan Medical University, Haikou, Hainan, China; Key Laboratory of Translational Tropical Medicine of Ministry of Education, Hainan Medical University, Haikou, Hainan, China.
  • 5 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • 6 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, China; and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region. Electronic address: kyyuen@hku.hk.
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 (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.

Keywords

Abiraterone; Abiraterone acetate (PubChem CID: 9821849); Antiviral; Bexarotene; Bexarotene (PubChem CID: 82146); COVID-19; Cetilistat; Cetilistat (PubChem CID: 9952916); Coronavirus; Diiodohydroxyquinoline; Diiodohydroxyquinoline (PubChem CID: 3728); Library; SARS-CoV-2; Treatment.

Figures
Products
Inhibitors & Agonists
Other Products