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A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes

Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis...

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Autores principales: Qian, Xi-Jing, Zhang, Xiao-Lian, Zhao, Ping, Jin, Yong-Sheng, Chen, Hai-Sheng, Xu, Qing-Qiang, Ren, Hao, Zhu, Shi-Ying, Tang, Hai-Lin, Zhu, Yong-Zhe, Qi, Zhong-Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890123/
https://www.ncbi.nlm.nih.gov/pubmed/27252043
http://dx.doi.org/10.1038/srep27268
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author Qian, Xi-Jing
Zhang, Xiao-Lian
Zhao, Ping
Jin, Yong-Sheng
Chen, Hai-Sheng
Xu, Qing-Qiang
Ren, Hao
Zhu, Shi-Ying
Tang, Hai-Lin
Zhu, Yong-Zhe
Qi, Zhong-Tian
author_facet Qian, Xi-Jing
Zhang, Xiao-Lian
Zhao, Ping
Jin, Yong-Sheng
Chen, Hai-Sheng
Xu, Qing-Qiang
Ren, Hao
Zhu, Shi-Ying
Tang, Hai-Lin
Zhu, Yong-Zhe
Qi, Zhong-Tian
author_sort Qian, Xi-Jing
collection PubMed
description Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations.
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spelling pubmed-48901232016-06-09 A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes Qian, Xi-Jing Zhang, Xiao-Lian Zhao, Ping Jin, Yong-Sheng Chen, Hai-Sheng Xu, Qing-Qiang Ren, Hao Zhu, Shi-Ying Tang, Hai-Lin Zhu, Yong-Zhe Qi, Zhong-Tian Sci Rep Article Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. Nature Publishing Group 2016-06-02 /pmc/articles/PMC4890123/ /pubmed/27252043 http://dx.doi.org/10.1038/srep27268 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Qian, Xi-Jing
Zhang, Xiao-Lian
Zhao, Ping
Jin, Yong-Sheng
Chen, Hai-Sheng
Xu, Qing-Qiang
Ren, Hao
Zhu, Shi-Ying
Tang, Hai-Lin
Zhu, Yong-Zhe
Qi, Zhong-Tian
A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title_full A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title_fullStr A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title_full_unstemmed A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title_short A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes
title_sort schisandra-derived compound schizandronic acid inhibits entry of pan-hcv genotypes into human hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890123/
https://www.ncbi.nlm.nih.gov/pubmed/27252043
http://dx.doi.org/10.1038/srep27268
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