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Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis

Influenza-associated pulmonary aspergillosis (IAPA) is a global recognized superinfection in critically ill influenza patients. Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is a newly approved anti-influenza therapeutic. Although the benefits as a treatment for influenza are clear, it...

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Autores principales: Seldeslachts, Laura, Jacobs, Cato, Tielemans, Birger, Vanhoffelen, Eliane, Van der Sloten, Lauren, Humblet-Baron, Stephanie, Naesens, Lieve, Lagrou, Katrien, Verbeken, Erik, Wauters, Joost, Vande Velde, Greetje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777735/
https://www.ncbi.nlm.nih.gov/pubmed/35049941
http://dx.doi.org/10.3390/jof8010001
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author Seldeslachts, Laura
Jacobs, Cato
Tielemans, Birger
Vanhoffelen, Eliane
Van der Sloten, Lauren
Humblet-Baron, Stephanie
Naesens, Lieve
Lagrou, Katrien
Verbeken, Erik
Wauters, Joost
Vande Velde, Greetje
author_facet Seldeslachts, Laura
Jacobs, Cato
Tielemans, Birger
Vanhoffelen, Eliane
Van der Sloten, Lauren
Humblet-Baron, Stephanie
Naesens, Lieve
Lagrou, Katrien
Verbeken, Erik
Wauters, Joost
Vande Velde, Greetje
author_sort Seldeslachts, Laura
collection PubMed
description Influenza-associated pulmonary aspergillosis (IAPA) is a global recognized superinfection in critically ill influenza patients. Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is a newly approved anti-influenza therapeutic. Although the benefits as a treatment for influenza are clear, its efficacy against an influenza-A. fumigatus co-infection has yet to be determined. We investigated the therapeutic effect of baloxavir marboxil in a murine model for IAPA. Immunocompetent mice received intranasal instillation of influenza A followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Administration of baloxavir marboxil or sham was started at day 0, day 2 or day 4. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (µCT) and fungal burden with bioluminescence imaging (BLI). In vivo imaging was supplemented with virological, mycological and biochemical endpoint investigations. We observed an improved body weight, survival and viral clearance in baloxavir marboxil treated mice. µCT showed less pulmonary lesions and bronchial dilation after influenza and after Aspergillus co-infection in a treatment-dependent pattern. Furthermore, baloxavir marboxil was associated with effective inhibition of fungal invasion. Hence, our results provide evidence that baloxavir marboxil mitigates severe influenza thereby decreasing the susceptibility to a lethal invasive Aspergillus superinfection.
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spelling pubmed-87777352022-01-22 Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis Seldeslachts, Laura Jacobs, Cato Tielemans, Birger Vanhoffelen, Eliane Van der Sloten, Lauren Humblet-Baron, Stephanie Naesens, Lieve Lagrou, Katrien Verbeken, Erik Wauters, Joost Vande Velde, Greetje J Fungi (Basel) Article Influenza-associated pulmonary aspergillosis (IAPA) is a global recognized superinfection in critically ill influenza patients. Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is a newly approved anti-influenza therapeutic. Although the benefits as a treatment for influenza are clear, its efficacy against an influenza-A. fumigatus co-infection has yet to be determined. We investigated the therapeutic effect of baloxavir marboxil in a murine model for IAPA. Immunocompetent mice received intranasal instillation of influenza A followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Administration of baloxavir marboxil or sham was started at day 0, day 2 or day 4. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (µCT) and fungal burden with bioluminescence imaging (BLI). In vivo imaging was supplemented with virological, mycological and biochemical endpoint investigations. We observed an improved body weight, survival and viral clearance in baloxavir marboxil treated mice. µCT showed less pulmonary lesions and bronchial dilation after influenza and after Aspergillus co-infection in a treatment-dependent pattern. Furthermore, baloxavir marboxil was associated with effective inhibition of fungal invasion. Hence, our results provide evidence that baloxavir marboxil mitigates severe influenza thereby decreasing the susceptibility to a lethal invasive Aspergillus superinfection. MDPI 2021-12-21 /pmc/articles/PMC8777735/ /pubmed/35049941 http://dx.doi.org/10.3390/jof8010001 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seldeslachts, Laura
Jacobs, Cato
Tielemans, Birger
Vanhoffelen, Eliane
Van der Sloten, Lauren
Humblet-Baron, Stephanie
Naesens, Lieve
Lagrou, Katrien
Verbeken, Erik
Wauters, Joost
Vande Velde, Greetje
Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title_full Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title_fullStr Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title_full_unstemmed Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title_short Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis
title_sort overcome double trouble: baloxavir marboxil suppresses influenza thereby mitigating secondary invasive pulmonary aspergillosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777735/
https://www.ncbi.nlm.nih.gov/pubmed/35049941
http://dx.doi.org/10.3390/jof8010001
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