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...

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Published inViruses Vol. 10; no. 11; p. 601
Main Authors Dong, Hui-Jun, Wang, Zhao-Hua, Meng, Wen, Li, Cui-Cui, Hu, Yan-Xin, Zhou, Lei, Wang, Xiao-Jia
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.11.2018
MDPI
Subjects
Antiviral activity
Antiviral agents
Antiviral drugs
Avian flu
Cell cycle
Dengue fever
Diarrhea
DNA virus
eIF4E
Genomes
Herpes simplex
Herpes viruses
HHT
Infections
Initiation factor eIF-4E
Kinases
Leukemia
mRNA
Newcastle disease
Phosphorylation
Polyclonal antibodies
Proteins
RNA virus
RNA viruses
Stomatitis
Transmissible gastroenteritis
Viral infections
viral replication
United States > US
China
viral replication
eIF4E
HHT
RNA virus
DNA virus
Online AccessGet full text
ISSN1999-4915
1999-4915
DOI10.3390/v10110601

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Abstract 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 (IC50) 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.
AbstractList 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 (IC50) 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.
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 ) 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.
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 (IC50) 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.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 (IC50) 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.
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.
Author Li, Cui-Cui
Meng, Wen
Wang, Xiao-Jia
Hu, Yan-Xin
Zhou, Lei
Dong, Hui-Jun
Wang, Zhao-Hua
AuthorAffiliation Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; donghuijun105@163.com (H.-J.D.); zhaohuaw26@163.com (Z.-H.W.); mengwen422fei@163.com (W.M.); piqiubang@163.com (C.-C.L.); huyx@cau.edu.cn (Y.-X.H.); leosj@cau.edu.cn (L.Z.)
AuthorAffiliation_xml – name: Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; donghuijun105@163.com (H.-J.D.); zhaohuaw26@163.com (Z.-H.W.); mengwen422fei@163.com (W.M.); piqiubang@163.com (C.-C.L.); huyx@cau.edu.cn (Y.-X.H.); leosj@cau.edu.cn (L.Z.)
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  surname: Dong
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  surname: Wang
  fullname: Wang, Xiao-Jia
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30388805$$D View this record in MEDLINE/PubMed
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Keywords viral replication
eIF4E
HHT
RNA virus
DNA virus
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Snippet To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the...
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SubjectTerms Antiviral activity
Antiviral agents
Antiviral drugs
Avian flu
Cell cycle
Dengue fever
Diarrhea
DNA virus
eIF4E
Genomes
Herpes simplex
Herpes viruses
HHT
Infections
Initiation factor eIF-4E
Kinases
Leukemia
mRNA
Newcastle disease
Phosphorylation
Polyclonal antibodies
Proteins
RNA virus
RNA viruses
Stomatitis
Transmissible gastroenteritis
Viral infections
viral replication
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Title The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo
URI https://www.ncbi.nlm.nih.gov/pubmed/30388805
https://www.proquest.com/docview/2582921141
https://www.proquest.com/docview/2129532785
https://pubmed.ncbi.nlm.nih.gov/PMC6266276
https://doaj.org/article/c7d42c7e6c83489db2ef9f5e9db7fbbd
Volume 10
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