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Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice

Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivitie...

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Autores principales: Dai, Wenwen, Bi, Jinpeng, Li, Fang, Wang, Shuai, Huang, Xinyu, Meng, Xiangyu, Sun, Bo, Wang, Deli, Kong, Wei, Jiang, Chunlai, Su, Weiheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669683/
https://www.ncbi.nlm.nih.gov/pubmed/31284698
http://dx.doi.org/10.3390/v11070625
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author Dai, Wenwen
Bi, Jinpeng
Li, Fang
Wang, Shuai
Huang, Xinyu
Meng, Xiangyu
Sun, Bo
Wang, Deli
Kong, Wei
Jiang, Chunlai
Su, Weiheng
author_facet Dai, Wenwen
Bi, Jinpeng
Li, Fang
Wang, Shuai
Huang, Xinyu
Meng, Xiangyu
Sun, Bo
Wang, Deli
Kong, Wei
Jiang, Chunlai
Su, Weiheng
author_sort Dai, Wenwen
collection PubMed
description Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures; however, to date, there are no reported data on their effects in animal models. In this study, we confirmed the in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in newborn mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development.
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spelling pubmed-66696832019-08-08 Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice Dai, Wenwen Bi, Jinpeng Li, Fang Wang, Shuai Huang, Xinyu Meng, Xiangyu Sun, Bo Wang, Deli Kong, Wei Jiang, Chunlai Su, Weiheng Viruses Article Enterovirus 71 (EV71) infection is known to cause hand, foot, and mouth disease (HFMD), which is associated with neurological complications; however, there is currently no effective treatment for this infection. Flavonoids are a large group of naturally occurring compounds with multiple bioactivities, and the inhibitory effects of several flavonoids against EV71 have been studied in cell cultures; however, to date, there are no reported data on their effects in animal models. In this study, we confirmed the in vitro activities of eight flavonoids against EV71 infection, based on the inhibition of cytopathic effects. Moreover, these flavonoids were found to reduce viral genomic RNA replication and protein synthesis. We further demonstrated the protective efficacy of these flavonoids in newborn mice challenged with a lethal dose of EV71. Apigenin, luteolin, kaempferol, formononetin, and penduletin conferred survival protection of 88.89%, 91.67%, 88.89%, 75%, and 66.67%, respectively, from the lethal EV71 challenge. In addition, isorhamnetin provided the highest mice survival protection of 100% at a dose of 10 mg/kg. This study, to the best of our knowledge, is the first to evaluate the in vivo anti-EV7l activities of multiple flavonoids, and we accordingly identified flavonoids as potential leading compounds for anti-EV71 drug development. MDPI 2019-07-07 /pmc/articles/PMC6669683/ /pubmed/31284698 http://dx.doi.org/10.3390/v11070625 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dai, Wenwen
Bi, Jinpeng
Li, Fang
Wang, Shuai
Huang, Xinyu
Meng, Xiangyu
Sun, Bo
Wang, Deli
Kong, Wei
Jiang, Chunlai
Su, Weiheng
Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title_full Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title_fullStr Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title_full_unstemmed Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title_short Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice
title_sort antiviral efficacy of flavonoids against enterovirus 71 infection in vitro and in newborn mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669683/
https://www.ncbi.nlm.nih.gov/pubmed/31284698
http://dx.doi.org/10.3390/v11070625
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