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The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo

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 heal...

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Autores principales: Schloer, Sebastian, Goretzko, Jonas, Kühnl, Alexander, Brunotte, Linda, Ludwig, Stephan, Rescher, Ursula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455256/
https://www.ncbi.nlm.nih.gov/pubmed/30866762
http://dx.doi.org/10.1080/22221751.2018.1559709
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author Schloer, Sebastian
Goretzko, Jonas
Kühnl, Alexander
Brunotte, Linda
Ludwig, Stephan
Rescher, Ursula
author_facet Schloer, Sebastian
Goretzko, Jonas
Kühnl, Alexander
Brunotte, Linda
Ludwig, Stephan
Rescher, Ursula
author_sort Schloer, Sebastian
collection PubMed
description 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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spelling pubmed-64552562019-04-18 The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo Schloer, Sebastian Goretzko, Jonas Kühnl, Alexander Brunotte, Linda Ludwig, Stephan Rescher, Ursula Emerg Microbes Infect Article 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. Taylor & Francis 2019-01-16 /pmc/articles/PMC6455256/ /pubmed/30866762 http://dx.doi.org/10.1080/22221751.2018.1559709 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Schloer, Sebastian
Goretzko, Jonas
Kühnl, Alexander
Brunotte, Linda
Ludwig, Stephan
Rescher, Ursula
The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455256/
https://www.ncbi.nlm.nih.gov/pubmed/30866762
http://dx.doi.org/10.1080/22221751.2018.1559709
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