The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo
ABSTRACTInfluenza A virus (IAV) is a common pathogen of respiratory disease. The IAV-induced seasonal epidemics and the sporadic pandemics are associated with high morbidity and mortality. Therefore, effective protection and therapy for IAV infections is an important challenge in countering this pub...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2018.1559709 |
| _version_ | 1797385751498850304 |
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| author | Sebastian Schloer Jonas Goretzko Alexander Kühnl Linda Brunotte Stephan Ludwig Ursula Rescher |
| author_facet | Sebastian Schloer Jonas Goretzko Alexander Kühnl Linda Brunotte Stephan Ludwig Ursula Rescher |
| author_sort | Sebastian Schloer |
| collection | DOAJ |
| description | ABSTRACTInfluenza A virus (IAV) is a common pathogen of respiratory disease. The IAV-induced seasonal epidemics and the sporadic pandemics are associated with high morbidity and mortality. Therefore, effective protection and therapy for IAV infections is an important challenge in countering this public health threat. Because vaccinations only protect against known circulating strains, and the currently available antivirals pose the risk of resistance formation, drugs targeting host cell factors needed for viral replication offer a promising therapeutic approach. In this study, we describe the use of the antifungal therapeutics posaconazole and itraconazole in the therapy of IAV. We show that both drugs efficiently inhibit the propagation of IAV in the cell culture model without being cytotoxic. The mode of action is probably based on several targets and includes both a priming of the interferon response and the induced imbalance of cellular cholesterol. The antiviral effect of itraconazole could be confirmed in the mouse model, where the administration of itraconazole led to a drastic reduction in mortality and a significant increase in the survival rate. Thus, our data indicate a promising therapeutic potential of at least itraconazole in influenza therapy. |
| first_indexed | 2024-03-08T21:58:47Z |
| format | Article |
| id | doaj.art-30def7bef94a4af185c7a339cd4abadd |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-08T21:58:47Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-30def7bef94a4af185c7a339cd4abadd2023-12-19T16:09:58ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-0181809310.1080/22221751.2018.1559709The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivoSebastian Schloer0Jonas Goretzko1Alexander Kühnl2Linda Brunotte3Stephan Ludwig4Ursula Rescher5Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Muenster, Muenster, GermanyInstitute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Muenster, Muenster, GermanyInstitute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Muenster, Muenster, GermanyInterdisciplinary Centre for Clinical Research, University of Muenster, Muenster, GermanyInterdisciplinary Centre for Clinical Research, University of Muenster, Muenster, GermanyInstitute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Muenster, Muenster, GermanyABSTRACTInfluenza A virus (IAV) is a common pathogen of respiratory disease. The IAV-induced seasonal epidemics and the sporadic pandemics are associated with high morbidity and mortality. Therefore, effective protection and therapy for IAV infections is an important challenge in countering this public health threat. Because vaccinations only protect against known circulating strains, and the currently available antivirals pose the risk of resistance formation, drugs targeting host cell factors needed for viral replication offer a promising therapeutic approach. In this study, we describe the use of the antifungal therapeutics posaconazole and itraconazole in the therapy of IAV. We show that both drugs efficiently inhibit the propagation of IAV in the cell culture model without being cytotoxic. The mode of action is probably based on several targets and includes both a priming of the interferon response and the induced imbalance of cellular cholesterol. The antiviral effect of itraconazole could be confirmed in the mouse model, where the administration of itraconazole led to a drastic reduction in mortality and a significant increase in the survival rate. Thus, our data indicate a promising therapeutic potential of at least itraconazole in influenza therapy.https://www.tandfonline.com/doi/10.1080/22221751.2018.1559709Influenza A virusposaconazoleitraconazoleinterferon responsecellular cholesterolhost cell factors |
| spellingShingle | Sebastian Schloer Jonas Goretzko Alexander Kühnl Linda Brunotte Stephan Ludwig Ursula Rescher The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo Emerging Microbes and Infections Influenza A virus posaconazole itraconazole interferon response cellular cholesterol host cell factors |
| title | The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| title_full | The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| title_fullStr | The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| title_full_unstemmed | The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| title_short | The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| title_sort | clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo |
| topic | Influenza A virus posaconazole itraconazole interferon response cellular cholesterol host cell factors |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2018.1559709 |
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