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In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses
Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599940/ https://www.ncbi.nlm.nih.gov/pubmed/33049959 http://dx.doi.org/10.3390/v12101139 |
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author | Checkmahomed, Liva Padey, Blandine Pizzorno, Andrés Terrier, Olivier Rosa-Calatrava, Manuel Abed, Yacine Baz, Mariana Boivin, Guy |
author_facet | Checkmahomed, Liva Padey, Blandine Pizzorno, Andrés Terrier, Olivier Rosa-Calatrava, Manuel Abed, Yacine Baz, Mariana Boivin, Guy |
author_sort | Checkmahomed, Liva |
collection | PubMed |
description | Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with several existing drugs, notably oseltamivir and favipiravir, to improve in vitro antiviral activity. These results should be considered for further animal and clinical evaluations. |
format | Online Article Text |
id | pubmed-7599940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75999402020-11-01 In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses Checkmahomed, Liva Padey, Blandine Pizzorno, Andrés Terrier, Olivier Rosa-Calatrava, Manuel Abed, Yacine Baz, Mariana Boivin, Guy Viruses Article Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with several existing drugs, notably oseltamivir and favipiravir, to improve in vitro antiviral activity. These results should be considered for further animal and clinical evaluations. MDPI 2020-10-08 /pmc/articles/PMC7599940/ /pubmed/33049959 http://dx.doi.org/10.3390/v12101139 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Checkmahomed, Liva Padey, Blandine Pizzorno, Andrés Terrier, Olivier Rosa-Calatrava, Manuel Abed, Yacine Baz, Mariana Boivin, Guy In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title | In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title_full | In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title_fullStr | In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title_full_unstemmed | In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title_short | In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses |
title_sort | in vitro combinations of baloxavir acid and other inhibitors against seasonal influenza a viruses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599940/ https://www.ncbi.nlm.nih.gov/pubmed/33049959 http://dx.doi.org/10.3390/v12101139 |
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