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Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo

Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-infl...

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Autores principales: Song, Eun-Jung, Españo, Erica, Shim, Sang-Mu, Nam, Jeong-Hyun, Kim, Jiyeon, Lee, Kiho, Park, Song-Kyu, Lee, Chong-Kil, Kim, Jeong-Ki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093218/
https://www.ncbi.nlm.nih.gov/pubmed/33941825
http://dx.doi.org/10.1038/s41598-021-88886-1
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author Song, Eun-Jung
Españo, Erica
Shim, Sang-Mu
Nam, Jeong-Hyun
Kim, Jiyeon
Lee, Kiho
Park, Song-Kyu
Lee, Chong-Kil
Kim, Jeong-Ki
author_facet Song, Eun-Jung
Españo, Erica
Shim, Sang-Mu
Nam, Jeong-Hyun
Kim, Jiyeon
Lee, Kiho
Park, Song-Kyu
Lee, Chong-Kil
Kim, Jeong-Ki
author_sort Song, Eun-Jung
collection PubMed
description Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza.
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spelling pubmed-80932182021-05-05 Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo Song, Eun-Jung Españo, Erica Shim, Sang-Mu Nam, Jeong-Hyun Kim, Jiyeon Lee, Kiho Park, Song-Kyu Lee, Chong-Kil Kim, Jeong-Ki Sci Rep Article Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza. Nature Publishing Group UK 2021-05-03 /pmc/articles/PMC8093218/ /pubmed/33941825 http://dx.doi.org/10.1038/s41598-021-88886-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Song, Eun-Jung
Españo, Erica
Shim, Sang-Mu
Nam, Jeong-Hyun
Kim, Jiyeon
Lee, Kiho
Park, Song-Kyu
Lee, Chong-Kil
Kim, Jeong-Ki
Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title_full Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title_fullStr Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title_full_unstemmed Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title_short Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo
title_sort inhibitory effects of aprotinin on influenza a and b viruses in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093218/
https://www.ncbi.nlm.nih.gov/pubmed/33941825
http://dx.doi.org/10.1038/s41598-021-88886-1
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