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The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo

Enterovirus 71 (EV71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. There is an urgent unmet medical need for new pharmaceutical agents to control EV71 infections. Using a multidisciplinary approach, we found that the approved...

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Autores principales: Ren, Peijun, Zou, Gang, Bailly, Benjamin, Xu, Shanshan, Zeng, Mei, Chen, Xinsheng, Shen, Liang, Zhang, Ying, Guillon, Patrice, Arenzana-Seisdedos, Fernando, Buchy, Philippe, Li, Jian, von Itzstein, Mark, Li, Qihan, Altmeyer, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185360/
https://www.ncbi.nlm.nih.gov/pubmed/26038755
http://dx.doi.org/10.1038/emi.2014.60
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author Ren, Peijun
Zou, Gang
Bailly, Benjamin
Xu, Shanshan
Zeng, Mei
Chen, Xinsheng
Shen, Liang
Zhang, Ying
Guillon, Patrice
Arenzana-Seisdedos, Fernando
Buchy, Philippe
Li, Jian
von Itzstein, Mark
Li, Qihan
Altmeyer, Ralf
author_facet Ren, Peijun
Zou, Gang
Bailly, Benjamin
Xu, Shanshan
Zeng, Mei
Chen, Xinsheng
Shen, Liang
Zhang, Ying
Guillon, Patrice
Arenzana-Seisdedos, Fernando
Buchy, Philippe
Li, Jian
von Itzstein, Mark
Li, Qihan
Altmeyer, Ralf
author_sort Ren, Peijun
collection PubMed
description Enterovirus 71 (EV71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. There is an urgent unmet medical need for new pharmaceutical agents to control EV71 infections. Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. Moreover, we demonstrate that when suramin is used in vivo at doses equivalent to or lower than the highest dose already used in humans, it significantly decreased mortality in mice challenged with a lethal dose of EV71 and peak viral load in adult rhesus monkeys. Thus, suramin inhibits EV71 infection by neutralizing virus particles prior to cell attachment. Consequently, these findings identify suramin as a clinical candidate for further development as a therapeutic or prophylactic treatment for severe EV71 infection.
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spelling pubmed-41853602014-10-16 The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo Ren, Peijun Zou, Gang Bailly, Benjamin Xu, Shanshan Zeng, Mei Chen, Xinsheng Shen, Liang Zhang, Ying Guillon, Patrice Arenzana-Seisdedos, Fernando Buchy, Philippe Li, Jian von Itzstein, Mark Li, Qihan Altmeyer, Ralf Emerg Microbes Infect Original Article Enterovirus 71 (EV71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. There is an urgent unmet medical need for new pharmaceutical agents to control EV71 infections. Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. Moreover, we demonstrate that when suramin is used in vivo at doses equivalent to or lower than the highest dose already used in humans, it significantly decreased mortality in mice challenged with a lethal dose of EV71 and peak viral load in adult rhesus monkeys. Thus, suramin inhibits EV71 infection by neutralizing virus particles prior to cell attachment. Consequently, these findings identify suramin as a clinical candidate for further development as a therapeutic or prophylactic treatment for severe EV71 infection. Nature Publishing Group 2014-09 2014-09-03 /pmc/articles/PMC4185360/ /pubmed/26038755 http://dx.doi.org/10.1038/emi.2014.60 Text en Copyright © 2014 Shanghai Shangyixun Cultural Communication Co., Ltd http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported 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/3.0/
spellingShingle Original Article
Ren, Peijun
Zou, Gang
Bailly, Benjamin
Xu, Shanshan
Zeng, Mei
Chen, Xinsheng
Shen, Liang
Zhang, Ying
Guillon, Patrice
Arenzana-Seisdedos, Fernando
Buchy, Philippe
Li, Jian
von Itzstein, Mark
Li, Qihan
Altmeyer, Ralf
The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title_full The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title_fullStr The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title_full_unstemmed The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title_short The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo
title_sort approved pediatric drug suramin identified as a clinical candidate for the treatment of ev71 infection—suramin inhibits ev71 infection in vitro and in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185360/
https://www.ncbi.nlm.nih.gov/pubmed/26038755
http://dx.doi.org/10.1038/emi.2014.60
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