Repurposing old drugs as antiviral agents for coronaviruses
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)....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Biomedical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2319417020300664 |
| _version_ | 1811212626175197184 |
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| author | Cheng-Wei Yang Tzu-Ting Peng Hsing-Yu Hsu Yue-Zhi Lee Szu-Huei Wu Wen-Hsing Lin Yi-Yu Ke Tsu-An Hsu Teng-Kuang Yeh Wen-Zheng Huang Jiunn-Horng Lin Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee |
| author_facet | Cheng-Wei Yang Tzu-Ting Peng Hsing-Yu Hsu Yue-Zhi Lee Szu-Huei Wu Wen-Hsing Lin Yi-Yu Ke Tsu-An Hsu Teng-Kuang Yeh Wen-Zheng Huang Jiunn-Horng Lin Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee |
| author_sort | Cheng-Wei Yang |
| collection | DOAJ |
| description | 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 (EC50) 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 EC50 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. |
| first_indexed | 2024-04-12T05:32:19Z |
| format | Article |
| id | doaj.art-4be953e501304c2898e31ca6eb2497df |
| institution | Directory Open Access Journal |
| issn | 2319-4170 |
| language | English |
| last_indexed | 2024-04-12T05:32:19Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedical Journal |
| spelling | doaj.art-4be953e501304c2898e31ca6eb2497df2022-12-22T03:46:01ZengElsevierBiomedical Journal2319-41702020-08-01434368374Repurposing old drugs as antiviral agents for coronavirusesCheng-Wei Yang0Tzu-Ting Peng1Hsing-Yu Hsu2Yue-Zhi Lee3Szu-Huei Wu4Wen-Hsing Lin5Yi-Yu Ke6Tsu-An Hsu7Teng-Kuang Yeh8Wen-Zheng Huang9Jiunn-Horng Lin10Huey-Kang Sytwu11Chiung-Tong Chen12Shiow-Ju Lee13Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan; Corresponding author. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Rd., Zhunan, Miaoli 350, Taiwan.Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan; Corresponding author. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Rd., Zhunan, Miaoli 350, Taiwan.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 (EC50) 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 EC50 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.http://www.sciencedirect.com/science/article/pii/S2319417020300664CoronavirusCOVID-19Cytopathic effectHCoV-OC43SARS-CoV-2Drug repurpose |
| spellingShingle | Cheng-Wei Yang Tzu-Ting Peng Hsing-Yu Hsu Yue-Zhi Lee Szu-Huei Wu Wen-Hsing Lin Yi-Yu Ke Tsu-An Hsu Teng-Kuang Yeh Wen-Zheng Huang Jiunn-Horng Lin Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee Repurposing old drugs as antiviral agents for coronaviruses Biomedical Journal Coronavirus COVID-19 Cytopathic effect HCoV-OC43 SARS-CoV-2 Drug repurpose |
| title | Repurposing old drugs as antiviral agents for coronaviruses |
| title_full | Repurposing old drugs as antiviral agents for coronaviruses |
| title_fullStr | Repurposing old drugs as antiviral agents for coronaviruses |
| title_full_unstemmed | Repurposing old drugs as antiviral agents for coronaviruses |
| title_short | Repurposing old drugs as antiviral agents for coronaviruses |
| title_sort | repurposing old drugs as antiviral agents for coronaviruses |
| topic | Coronavirus COVID-19 Cytopathic effect HCoV-OC43 SARS-CoV-2 Drug repurpose |
| url | http://www.sciencedirect.com/science/article/pii/S2319417020300664 |
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