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Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus
Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal ac...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638965/ https://www.ncbi.nlm.nih.gov/pubmed/29026122 http://dx.doi.org/10.1038/s41598-017-13316-0 |
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author | Hu, Che-Ming Jack Chang, Wei-Shan Fang, Zih-Syun Chen, You-Ting Wang, Wen-Lin Tsai, Hsiao-Han Chueh, Ling-Ling Takano, Tomomi Hohdatsu, Tsutomu Chen, Hui-Wen |
author_facet | Hu, Che-Ming Jack Chang, Wei-Shan Fang, Zih-Syun Chen, You-Ting Wang, Wen-Lin Tsai, Hsiao-Han Chueh, Ling-Ling Takano, Tomomi Hohdatsu, Tsutomu Chen, Hui-Wen |
author_sort | Hu, Che-Ming Jack |
collection | PubMed |
description | Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious peritonitis virus (FIPV). Experimental results show that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells, alters the cellular susceptibility to FIPV, and inhibits the downstream virus replication. In addition, diphyllin delivered by polymeric nanoparticles consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) further demonstrates an improved safety profile and enhanced inhibitory activity against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin nanoparticles showed a prominent antiviral effect against the feline coronavirus. In addition, the diphyllin nanoparticles were well tolerated in mice following high-dose intravenous administration. This study highlights the therapeutic potential of diphyllin and its nanoformulation for the treatment of FIP. |
format | Online Article Text |
id | pubmed-5638965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56389652017-10-18 Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus Hu, Che-Ming Jack Chang, Wei-Shan Fang, Zih-Syun Chen, You-Ting Wang, Wen-Lin Tsai, Hsiao-Han Chueh, Ling-Ling Takano, Tomomi Hohdatsu, Tsutomu Chen, Hui-Wen Sci Rep Article Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious peritonitis virus (FIPV). Experimental results show that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells, alters the cellular susceptibility to FIPV, and inhibits the downstream virus replication. In addition, diphyllin delivered by polymeric nanoparticles consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) further demonstrates an improved safety profile and enhanced inhibitory activity against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV infection, diphyllin nanoparticles showed a prominent antiviral effect against the feline coronavirus. In addition, the diphyllin nanoparticles were well tolerated in mice following high-dose intravenous administration. This study highlights the therapeutic potential of diphyllin and its nanoformulation for the treatment of FIP. Nature Publishing Group UK 2017-10-12 /pmc/articles/PMC5638965/ /pubmed/29026122 http://dx.doi.org/10.1038/s41598-017-13316-0 Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hu, Che-Ming Jack Chang, Wei-Shan Fang, Zih-Syun Chen, You-Ting Wang, Wen-Lin Tsai, Hsiao-Han Chueh, Ling-Ling Takano, Tomomi Hohdatsu, Tsutomu Chen, Hui-Wen Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title | Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title_full | Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title_fullStr | Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title_full_unstemmed | Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title_short | Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
title_sort | nanoparticulate vacuolar atpase blocker exhibits potent host-targeted antiviral activity against feline coronavirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638965/ https://www.ncbi.nlm.nih.gov/pubmed/29026122 http://dx.doi.org/10.1038/s41598-017-13316-0 |
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