Journal
EMERGING MICROBES & INFECTIONS
Volume 8, Issue 1, Pages 80-93Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2018.1559709
Keywords
Influenza A virus; posaconazole; itraconazole; interferon response; cellular cholesterol; host cell factors; mouse model; drug repurposing
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Funding
- Interdisciplinary Center of Clinical Research of the Munster Medical School (IZKF) [RE2/026/15, Lud2/008/17]
- German Research Foundation (DFG) [SFB1009/A06, SFB1348/A11, GRK 1409, SFB1009/B02, Lu477/23-1]
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Influenza 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.
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