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  1. Article ; Online: Human IVIG treatment in a neurological disease model for Enterovirus A71 infection in 28-day-old AG129 mice.

    Peterson, Christopher J / Hurst, Brett L / Evans, W Joseph / Van Wettere, Arnaud J / Gibson, Scott A / Smee, Donald F / Tarbet, E Bart

    Virology

    2023  Volume 580, Page(s) 62–72

    Abstract: Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we ... ...

    Abstract Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we report the development of an EV-A71 model in 28-day-old mice. Virus was serially passaged until it produced consistent lethality and rear-limb paralysis. Onset of disease occurred between days 6-9 post-infection, with mortality following weight loss and neurological signs on days 9-14. In addition, a single administration of human intravenous immunoglobulin at doses of 200, 400 and 800 mg/kg at 4h post-infection was evaluated in the model. Protection from weight loss, neurological signs, and mortality (between 50 and 89%) were observed at doses of 400 mg/kg or greater. Based on these results, IVIG was selected for use as a positive control in this acute model, and suggest that IVIG is a potential therapeutic for EV-A71 infections.
    MeSH term(s) Child ; Humans ; Mice ; Animals ; Child, Preschool ; Immunoglobulins, Intravenous/therapeutic use ; Enterovirus Infections ; Enterovirus ; Enterovirus A, Human ; Nervous System Diseases ; Disease Models, Animal
    Chemical Substances Immunoglobulins, Intravenous
    Language English
    Publishing date 2023-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.172: Show issues Location:
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  2. Article ; Online: Human IVIG treatment in a neurological disease model for Enterovirus A71 infection in 28-day-old AG129 mice

    Peterson, Christopher J. / Hurst, Brett L. / Evans, W. Joseph / Van Wettere, Arnaud J. / Gibson, Scott A. / Smee, Donald F. / Tarbet, E. Bart

    Virology. 2023 Feb. 04,

    2023  

    Abstract: Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we ... ...

    Abstract Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we report the development of an EV-A71 model in 28-day-old mice. Virus was serially passaged until it produced consistent lethality and rear-limb paralysis. Onset of disease occurred between days 6–9 post-infection, with mortality following weight loss and neurological signs on days 9–14. In addition, a single administration of human intravenous immunoglobulin at doses of 200, 400 and 800 mg/kg at 4h post-infection was evaluated in the model. Protection from weight loss, neurological signs, and mortality (between 50-89%) were observed at doses of 400 mg/kg or greater. Based on these results, IVIG was selected for use as a positive control in this acute model, and suggest that IVIG is a potential therapeutic for EV-A71 infections.
    Keywords Enterovirus A ; death ; disease models ; humans ; immunoglobulins ; intravenous injection ; mortality ; nervous system diseases ; paralysis ; virology ; viruses ; weight loss ; Enterovirus A71 ; Animal model ; Neurological disease ; AG129 ; Intravenous immunoglobulin ; Therapeutics
    Language English
    Dates of publication 2023-0204
    Size p. 62-72.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.02.002
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  3. Article ; Online: Evaluation of antiviral therapies in respiratory and neurological disease models of Enterovirus D68 infection in mice.

    Hurst, Brett L / Evans, W Joseph / Smee, Donald F / Van Wettere, Arnaud J / Tarbet, E Bart

    Virology

    2018  Volume 526, Page(s) 146–154

    Abstract: Enterovirus D68 (EV-D68) is unique among enteroviruses because of the ability to cause severe respiratory disease as well as neurological disease. We developed separate models of respiratory and neurological disease following EV-D68 infection in AG129 ... ...

    Abstract Enterovirus D68 (EV-D68) is unique among enteroviruses because of the ability to cause severe respiratory disease as well as neurological disease. We developed separate models of respiratory and neurological disease following EV-D68 infection in AG129 mice that respond to antiviral treatment with guanidine. In four-week-old mice infected intranasally, EV-D68 replicates to high titers in lung tissue increasing the proinflammatory cytokines MCP-1 and IL-6. The respiratory infection also produces an acute viremia. In 10-day-old mice infected intraperitoneally, EV-D68 causes a neurological disease with weight-loss, paralysis, and mortality. In our respiratory model, treatment with guanidine provides a two-log reduction in lung virus titers, reduces MCP-1 and IL-6, and prevents histological lesions in the lungs. Importantly, viremia is prevented by early treatment with guanidine. In our neurological model, guanidine treatment protects mice from weight-loss, paralysis, and mortality. These results demonstrate the utility of these models for evaluation of antiviral therapies for EV-D68 infection.
    MeSH term(s) Animals ; Antiviral Agents/therapeutic use ; Cytokines/metabolism ; Disease Models, Animal ; Enterovirus D, Human ; Enterovirus Infections/drug therapy ; Enterovirus Infections/pathology ; Enterovirus Infections/physiopathology ; Enterovirus Infections/virology ; Female ; Guanidine/therapeutic use ; Humans ; Lung/metabolism ; Lung/pathology ; Lung/physiopathology ; Lung/virology ; Male ; Mice ; Nervous System Diseases/drug therapy ; Nervous System Diseases/pathology ; Nervous System Diseases/physiopathology ; Nervous System Diseases/virology ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/pathology ; Respiratory Tract Infections/physiopathology ; Respiratory Tract Infections/virology ; Treatment Outcome ; Viral Load/drug effects ; Viremia/prevention & control
    Chemical Substances Antiviral Agents ; Cytokines ; Guanidine (JU58VJ6Y3B)
    Language English
    Publishing date 2018-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2018.10.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.172: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  4. Article ; Online: Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.

    Smee, Donald F / Evans, W Joseph / Nicolaou, K C / Tarbet, E Bart / Day, Craig W

    Antiviral research

    2016  Volume 131, Page(s) 61–65

    Abstract: Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71) ...

    Abstract Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents (enviroxime, guanidine HCl, pirodavir, pleconaril, and rupintrivir), nucleobase/nucleoside analogs (3-deazaguanine and ribavirin), and three novel epidithiodiketopiperazines (KCN-2,2'-epi-19, KCN-19, and KCN-21). Of these, rupintrivir was the most potent, with 50% inhibition of viral cytopathic effect (EC50) and 90% inhibition (EC90) of virus yield at 0.0022-0.0053 μM against EV-D68. Enviroxime, pleconaril and the KCN compounds showed efficacy at 0.01-0.3 μM; 3-deazaguanine and pirodavir inhibited EV-D68 at 7-13 μM, and guanidine HCl and ribavirin were inhibitory at 80-135 μM. Pirodavir was active against EV-71 (EC50 of 0.78 μM) but not against RV-87 or EV-D68, and all other compounds were less effective against EV-71 than against RV-87 and EV-D68. The most promising compound inhibiting both virus infections at low concentrations was rupintrivir. Antiviral activity was confirmed for the ten compounds in virus yield reduction (VYR) assays in RD cells, and for enviroxime, guanidine HCl, and pirodavir by cytopathic effect (CPE) assays in A549, HeLa-Ohio-1, and RD cells. These studies may serve as a basis for further pre-clinical discovery of anti-enterovirus inhibitors. Furthermore, the antiviral profiles and growth characteristics observed herein support the assertion that EV-D68 should be classified together with RV-87.
    MeSH term(s) A549 Cells ; Antimetabolites/pharmacology ; Antiviral Agents/pharmacology ; Benzimidazoles/pharmacology ; Enterovirus A, Human/drug effects ; Enterovirus A, Human/growth & development ; Enterovirus D, Human/drug effects ; Enterovirus D, Human/growth & development ; Guanine/analogs & derivatives ; Guanine/pharmacology ; HeLa Cells ; Humans ; Oxadiazoles/pharmacology ; Picornaviridae/drug effects ; Piperazines/pharmacology ; Piperidines/pharmacology ; Pyridazines/pharmacology ; Rhabdomyosarcoma ; Rhinovirus/drug effects ; Rhinovirus/growth & development ; Ribavirin/pharmacology
    Chemical Substances Antimetabolites ; Antiviral Agents ; Benzimidazoles ; Oxadiazoles ; Piperazines ; Piperidines ; Pyridazines ; epidithiodioxopiperazine ; enviroxime (133013L556) ; Ribavirin (49717AWG6K) ; Guanine (5Z93L87A1R) ; 3-deazaguanine (9DRB973HUI) ; pleconaril (9H4570Q89D) ; pirodavir (BML697718K)
    Language English
    Publishing date 2016-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2016.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1627: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Development of a respiratory disease model for enterovirus D68 in 4-week-old mice for evaluation of antiviral therapies.

    Evans, W Joseph / Hurst, Brett L / Peterson, Christopher J / Van Wettere, Arnaud J / Day, Craig W / Smee, Donald F / Tarbet, E Bart

    Antiviral research

    2018  Volume 162, Page(s) 61–70

    Abstract: Enterovirus D68 (EV-D68) is a non-polio enterovirus that affects the respiratory system and can cause serious complications, especially in children and older people with weakened immune systems. As an emerging virus, there are no current antiviral ... ...

    Abstract Enterovirus D68 (EV-D68) is a non-polio enterovirus that affects the respiratory system and can cause serious complications, especially in children and older people with weakened immune systems. As an emerging virus, there are no current antiviral therapies or vaccines available. Our goal was to develop a mouse model of human EV-D68 infection that mimicked the disease observed in humans and could be used for evaluation of experimental therapeutics. This is the first report of a respiratory disease model for EV-D68 infection in mice. We adapted the virus by 30 serial passages in AG129 mice, which are deficient in IFN- α/β and -γ receptors. Despite a lack of weight loss or mortality in mice, lung function measured by plethysmography, showed an increase in enhanced pause (Penh) on days 6 and 7 post-infection. In addition, as virus adapted to mice, virus titer in the lungs increased 50-fold, and the pro-inflammatory cytokines MCP-1 and RANTES increased 15-fold and 2-fold in the lung, respectively. In addition, a time course of mouse-adapted EV-D68 infection was determined in lung, blood, liver, kidney, spleen, leg muscle, spinal cord and brain. Virus in the lung replicated rapidly after intranasal inoculation of adapted virus, 10
    MeSH term(s) Animals ; Antiviral Agents/therapeutic use ; Chemokines/immunology ; Cytokines/immunology ; Disease Models, Animal ; Enterovirus D, Human ; Enterovirus Infections/drug therapy ; Enterovirus Infections/immunology ; Enterovirus Infections/virology ; Female ; Lung/virology ; Male ; Mice ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/immunology ; Respiratory Tract Infections/virology ; Viral Load ; Viremia
    Chemical Substances Antiviral Agents ; Chemokines ; Cytokines
    Language English
    Publishing date 2018-12-03
    Publishing country Netherlands
    Document type Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2018.11.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1627: Show issues Location:
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  6. Article ; Online: Evaluation of cell viability dyes in antiviral assays with RNA viruses that exhibit different cytopathogenic properties.

    Smee, Donald F / Hurst, Brett L / Evans, W Joseph / Clyde, Nathan / Wright, Sean / Peterson, Christopher / Jung, Kie-Hoon / Day, Craig W

    Journal of virological methods

    2017  Volume 246, Page(s) 51–57

    Abstract: Studies were conducted to determine the performance of four dyes in assessing antiviral activities of compounds against three RNA viruses with differing cytopathogenic properties. Dyes included ... ...

    Abstract Studies were conducted to determine the performance of four dyes in assessing antiviral activities of compounds against three RNA viruses with differing cytopathogenic properties. Dyes included alamarBlue
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Cell Survival/drug effects ; Chikungunya virus/drug effects ; Chikungunya virus/pathogenicity ; Chikungunya virus/physiology ; Chlorocebus aethiops ; Coloring Agents/chemistry ; Cytopathogenic Effect, Viral ; Dengue Virus/drug effects ; Dengue Virus/pathogenicity ; Dengue Virus/physiology ; Junin virus/drug effects ; Junin virus/pathogenicity ; Junin virus/physiology ; Oxazines ; RNA Viruses/drug effects ; RNA Viruses/pathogenicity ; RNA Viruses/physiology ; Vero Cells ; Virus Replication/drug effects ; Viruses/drug effects ; Xanthenes
    Chemical Substances Antiviral Agents ; Coloring Agents ; Oxazines ; Xanthenes ; resazurin (1FN9YD6968)
    Language English
    Publishing date 2017-03-27
    Publishing country Netherlands
    Document type Evaluation Study ; Journal Article
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2017.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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