Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum...
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| Format: | Artykuł |
| Język: | English |
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MDPI AG
2020-06-01
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| Seria: | Viruses |
| Hasła przedmiotowe: | |
| Dostęp online: | https://www.mdpi.com/1999-4915/12/6/628 |
| _version_ | 1827715311286091776 |
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| author | Shuofeng Yuan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Jessica Oi-Ling Tsang Ronghui Liang Jianli Cao Kaiming Tang Jian-Piao Cai Zi-Wei Ye Feifei Yin Kelvin Kai-Wang To Hin Chu Dong-Yan Jin Ivan Fan-Ngai Hung Kwok-Yung Yuen Jasper Fuk-Woo Chan |
| author_facet | Shuofeng Yuan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Jessica Oi-Ling Tsang Ronghui Liang Jianli Cao Kaiming Tang Jian-Piao Cai Zi-Wei Ye Feifei Yin Kelvin Kai-Wang To Hin Chu Dong-Yan Jin Ivan Fan-Ngai Hung Kwok-Yung Yuen Jasper Fuk-Woo Chan |
| author_sort | Shuofeng Yuan |
| collection | DOAJ |
| description | The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC<sub>50</sub> at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials. |
| first_indexed | 2024-03-10T19:15:29Z |
| format | Article |
| id | doaj.art-e3988b2d68314525a898ef675400293b |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T19:15:29Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e3988b2d68314525a898ef675400293b2023-11-20T03:27:36ZengMDPI AGViruses1999-49152020-06-0112662810.3390/v12060628Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)Shuofeng Yuan0Chris Chun-Yiu Chan1Kenn Ka-Heng Chik2Jessica Oi-Ling Tsang3Ronghui Liang4Jianli Cao5Kaiming Tang6Jian-Piao Cai7Zi-Wei Ye8Feifei Yin9Kelvin Kai-Wang To10Hin Chu11Dong-Yan Jin12Ivan Fan-Ngai Hung13Kwok-Yung Yuen14Jasper Fuk-Woo Chan15State 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaHainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDivision of Infectious Diseases, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState 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, Hong Kong, ChinaState 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, Hong Kong, ChinaThe ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC<sub>50</sub> at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.https://www.mdpi.com/1999-4915/12/6/628coronavirusCOVID-19interferonAM58025-hydroxycholesteroltreatment |
| spellingShingle | Shuofeng Yuan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Jessica Oi-Ling Tsang Ronghui Liang Jianli Cao Kaiming Tang Jian-Piao Cai Zi-Wei Ye Feifei Yin Kelvin Kai-Wang To Hin Chu Dong-Yan Jin Ivan Fan-Ngai Hung Kwok-Yung Yuen Jasper Fuk-Woo Chan Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) Viruses coronavirus COVID-19 interferon AM580 25-hydroxycholesterol treatment |
| title | Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) |
| title_full | Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) |
| title_fullStr | Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) |
| title_full_unstemmed | Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) |
| title_short | Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) |
| title_sort | broad spectrum host based antivirals targeting the interferon and lipogenesis pathways as potential treatment options for the pandemic coronavirus disease 2019 covid 19 |
| topic | coronavirus COVID-19 interferon AM580 25-hydroxycholesterol treatment |
| url | https://www.mdpi.com/1999-4915/12/6/628 |
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