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Open AccessArticle

Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection

1
Institute 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, Germany
2
Institute of Medical Virology, Justus-Liebig-Universität, Schuberststr. 81, D-35392 Gießen, Germany
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Institute of Virology (IVM) and “Cells in Motion” Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(7), 703; https://doi.org/10.3390/v12070703
Received: 27 May 2020 / Revised: 25 June 2020 / Accepted: 26 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Antiviral Drug Combinations)
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. View Full-Text
Keywords: influenza A virus; oseltamivir; itraconazole; host-directed therapy; drug repurposing; combination therapy; additivity influenza A virus; oseltamivir; itraconazole; host-directed therapy; drug repurposing; combination therapy; additivity
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MDPI and ACS Style

Schloer, S.; Goretzko, J.; Pleschka, S.; Ludwig, S.; Rescher, U. Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection. Viruses 2020, 12, 703.

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