An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality

Human infections caused by avian influenza A virus type subtype H7N9 have been associated with substantial morbidity and mortality. Emergence of virus variants carrying markers of decreased susceptibility to neuraminidase inhibitors was reported. Here we show that DAS181 (Fludase), an antiviral drug...

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Autores principales: Marjuki, Henju, Mishin, Vasiliy P., Chesnokov, Anton P., De La Cruz, Juan A., Fry, Alicia M., Villanueva, Julie, Gubareva, Larisa V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091581/
https://www.ncbi.nlm.nih.gov/pubmed/24569063
http://dx.doi.org/10.1093/infdis/jiu105
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author Marjuki, Henju
Mishin, Vasiliy P.
Chesnokov, Anton P.
De La Cruz, Juan A.
Fry, Alicia M.
Villanueva, Julie
Gubareva, Larisa V.
author_facet Marjuki, Henju
Mishin, Vasiliy P.
Chesnokov, Anton P.
De La Cruz, Juan A.
Fry, Alicia M.
Villanueva, Julie
Gubareva, Larisa V.
author_sort Marjuki, Henju
collection PubMed
description Human infections caused by avian influenza A virus type subtype H7N9 have been associated with substantial morbidity and mortality. Emergence of virus variants carrying markers of decreased susceptibility to neuraminidase inhibitors was reported. Here we show that DAS181 (Fludase), an antiviral drug with sialidase activity, potently inhibited replication of wild-type influenza A(H7N9) and its oseltamivir-resistant R292K variants in mice. A once-daily administration initiated early after lethal infection hampered body weight loss and completely protected mice from lethality. We observed a time-dependent effect for 24–72-hour delayed DAS181 treatments on morbidity and mortality. The results warrant further investigation of DAS181 for influenza treatment.
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spelling pubmed-40915812014-07-10 An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality Marjuki, Henju Mishin, Vasiliy P. Chesnokov, Anton P. De La Cruz, Juan A. Fry, Alicia M. Villanueva, Julie Gubareva, Larisa V. J Infect Dis Major Articles and Brief Reports Human infections caused by avian influenza A virus type subtype H7N9 have been associated with substantial morbidity and mortality. Emergence of virus variants carrying markers of decreased susceptibility to neuraminidase inhibitors was reported. Here we show that DAS181 (Fludase), an antiviral drug with sialidase activity, potently inhibited replication of wild-type influenza A(H7N9) and its oseltamivir-resistant R292K variants in mice. A once-daily administration initiated early after lethal infection hampered body weight loss and completely protected mice from lethality. We observed a time-dependent effect for 24–72-hour delayed DAS181 treatments on morbidity and mortality. The results warrant further investigation of DAS181 for influenza treatment. Oxford University Press 2014-08-01 2014-02-25 /pmc/articles/PMC4091581/ /pubmed/24569063 http://dx.doi.org/10.1093/infdis/jiu105 Text en © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle Major Articles and Brief Reports
Marjuki, Henju
Mishin, Vasiliy P.
Chesnokov, Anton P.
De La Cruz, Juan A.
Fry, Alicia M.
Villanueva, Julie
Gubareva, Larisa V.
An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title_full An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title_fullStr An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title_full_unstemmed An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title_short An Investigational Antiviral Drug, DAS181, Effectively Inhibits Replication of Zoonotic Influenza A Virus Subtype H7N9 and Protects Mice From Lethality
title_sort investigational antiviral drug, das181, effectively inhibits replication of zoonotic influenza a virus subtype h7n9 and protects mice from lethality
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091581/
https://www.ncbi.nlm.nih.gov/pubmed/24569063
http://dx.doi.org/10.1093/infdis/jiu105
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