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The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo
To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266276/ https://www.ncbi.nlm.nih.gov/pubmed/30388805 http://dx.doi.org/10.3390/v10110601 |
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author | Dong, Hui-Jun Wang, Zhao-Hua Meng, Wen Li, Cui-Cui Hu, Yan-Xin Zhou, Lei Wang, Xiao-Jia |
author_facet | Dong, Hui-Jun Wang, Zhao-Hua Meng, Wen Li, Cui-Cui Hu, Yan-Xin Zhou, Lei Wang, Xiao-Jia |
author_sort | Dong, Hui-Jun |
collection | PubMed |
description | To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC(50)) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals. |
format | Online Article Text |
id | pubmed-6266276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62662762018-12-07 The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo Dong, Hui-Jun Wang, Zhao-Hua Meng, Wen Li, Cui-Cui Hu, Yan-Xin Zhou, Lei Wang, Xiao-Jia Viruses Article To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC(50)) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals. MDPI 2018-11-01 /pmc/articles/PMC6266276/ /pubmed/30388805 http://dx.doi.org/10.3390/v10110601 Text en © 2018 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 Dong, Hui-Jun Wang, Zhao-Hua Meng, Wen Li, Cui-Cui Hu, Yan-Xin Zhou, Lei Wang, Xiao-Jia The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title | The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title_full | The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title_fullStr | The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title_full_unstemmed | The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title_short | The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo |
title_sort | natural compound homoharringtonine presents broad antiviral activity in vitro and in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266276/ https://www.ncbi.nlm.nih.gov/pubmed/30388805 http://dx.doi.org/10.3390/v10110601 |
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