國家衛生研究院 NHRI:Item 3990099045/12725

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12725

Title:	Repurposing old drugs as antiviral agents for coronaviruses
Authors:	Yang, CW;Peng, TT;Hsu, HY;Lee, YZ;Wu, SH;Lin, WH;Ke, YY;Hsu, TA;Yeh, TK;Huang, WZ;Lin, JH;Sytwu, HK;Chen, CT;Lee, SJ
Contributors:	Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology
Abstract:	BACKGROUND: New therapeutic options to address the ongoing coronavirus disease 2019 (COVID-19) pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC(50)) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC(50) values ranging from 11 nM to 75 μM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, and vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.
Date:	2020-08
Relation:	Biomedical Journal. 2020 Aug;43(4):368-374.
Link to:	http://dx.doi.org/10.1016/j.bj.2020.05.003
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2319-4170&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000579445300011
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85086510043
Appears in Collections:	[Shiow-Ju Lee] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [John Tsu-An Hsu] Periodical Articles [Huey-Kang Sytwu] Periodical Articles

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