Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection
Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging vir...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/7/703 |
| _version_ | 1797563804876275712 |
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| author | Sebastian Schloer Jonas Goretzko Stephan Pleschka Stephan Ludwig Ursula Rescher |
| author_facet | Sebastian Schloer Jonas Goretzko Stephan Pleschka Stephan Ludwig Ursula Rescher |
| author_sort | Sebastian Schloer |
| collection | DOAJ |
| description | Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus-host interactions is a new and emerging field, and therapies based on the combination of virus- and host-directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho-epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance. |
| first_indexed | 2024-03-10T18:48:21Z |
| format | Article |
| id | doaj.art-62f9580c45304b9bbf68cacee7b704da |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T18:48:21Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-62f9580c45304b9bbf68cacee7b704da2023-11-20T05:20:49ZengMDPI AGViruses1999-49152020-06-0112770310.3390/v12070703Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus InfectionSebastian Schloer0Jonas Goretzko1Stephan Pleschka2Stephan Ludwig3Ursula Rescher4Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, GermanyInstitute of Medical Biochemistry, Center for Molecular Biology of Inflammation and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, GermanyInstitute of Medical Virology, Justus-Liebig-Universität, Schuberststr. 81, D-35392 Gießen, GermanyInstitute of Virology (IVM) and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, GermanyInstitute of Medical Biochemistry, Center for Molecular Biology of Inflammation and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, GermanyInfluenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus-host interactions is a new and emerging field, and therapies based on the combination of virus- and host-directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho-epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance.https://www.mdpi.com/1999-4915/12/7/703influenza A virusoseltamiviritraconazolehost-directed therapydrug repurposingcombination therapy |
| spellingShingle | Sebastian Schloer Jonas Goretzko Stephan Pleschka Stephan Ludwig Ursula Rescher Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection Viruses influenza A virus oseltamivir itraconazole host-directed therapy drug repurposing combination therapy |
| title | Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection |
| title_full | Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection |
| title_fullStr | Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection |
| title_full_unstemmed | Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection |
| title_short | Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection |
| title_sort | combinatory treatment with oseltamivir and itraconazole targeting both virus and host factors in influenza a virus infection |
| topic | influenza A virus oseltamivir itraconazole host-directed therapy drug repurposing combination therapy |
| url | https://www.mdpi.com/1999-4915/12/7/703 |
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