Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV)...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/4/651 |
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| author | Meehyun Ko So Young Chang Soo Young Byun Aleksandr Ianevski Inhee Choi Anne-Laure Pham Hung d’Alexandry d’Orengiani Erlend Ravlo Wei Wang Magnar Bjørås Denis E. Kainov David Shum Ji-Young Min Marc P. Windisch |
| author_facet | Meehyun Ko So Young Chang Soo Young Byun Aleksandr Ianevski Inhee Choi Anne-Laure Pham Hung d’Alexandry d’Orengiani Erlend Ravlo Wei Wang Magnar Bjørås Denis E. Kainov David Shum Ji-Young Min Marc P. Windisch |
| author_sort | Meehyun Ko |
| collection | DOAJ |
| description | Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses. |
| first_indexed | 2024-03-10T12:27:33Z |
| format | Article |
| id | doaj.art-f21ab46b682142fdb986507f13718ee8 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T12:27:33Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f21ab46b682142fdb986507f13718ee82023-11-21T14:56:18ZengMDPI AGViruses1999-49152021-04-0113465110.3390/v13040651Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19Meehyun Ko0So Young Chang1Soo Young Byun2Aleksandr Ianevski3Inhee Choi4Anne-Laure Pham Hung d’Alexandry d’Orengiani5Erlend Ravlo6Wei Wang7Magnar Bjørås8Denis E. Kainov9David Shum10Ji-Young Min11Marc P. Windisch12Respiratory Virus Laboratory, Emerging Virus Group, Discovery Biology Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaRespiratory Virus Laboratory, Emerging Virus Group, Discovery Biology Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaScreening Discovery Platform, Translation Research Division, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayMedicinal Chemistry, Medicinal Chemistry & Business Development Group, Translational Research Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaRespiratory Virus Laboratory, Emerging Virus Group, Discovery Biology Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayScreening Discovery Platform, Translation Research Division, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaRespiratory Virus Laboratory, Emerging Virus Group, Discovery Biology Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaApplied Molecular Virology Laboratory, Unmet Medical Needs Group, Discovery Biology Department, Institut Pasteur Korea, Seongnam 13488, Gyeonggi, KoreaTherapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.https://www.mdpi.com/1999-4915/13/4/651Middle East respiratory syndrome coronavirussevere acute respiratory syndrome coronavirus diseaseclinical isolatehigh-content screeningFDA-approved drugsdrug repurposing |
| spellingShingle | Meehyun Ko So Young Chang Soo Young Byun Aleksandr Ianevski Inhee Choi Anne-Laure Pham Hung d’Alexandry d’Orengiani Erlend Ravlo Wei Wang Magnar Bjørås Denis E. Kainov David Shum Ji-Young Min Marc P. Windisch Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 Viruses Middle East respiratory syndrome coronavirus severe acute respiratory syndrome coronavirus disease clinical isolate high-content screening FDA-approved drugs drug repurposing |
| title | Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 |
| title_full | Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 |
| title_fullStr | Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 |
| title_full_unstemmed | Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 |
| title_short | Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19 |
| title_sort | screening of fda approved drugs using a mers cov clinical isolate from south korea identifies potential therapeutic options for covid 19 |
| topic | Middle East respiratory syndrome coronavirus severe acute respiratory syndrome coronavirus disease clinical isolate high-content screening FDA-approved drugs drug repurposing |
| url | https://www.mdpi.com/1999-4915/13/4/651 |
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