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Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox

The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeu...

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Autores principales: Parker, Scott, Chen, Nanhai G., Foster, Scott, Hartzler, Hollyce, Hembrador, Ed, Hruby, Dennis, Jordan, Robert, Lanier, Randall, Painter, George, Painter, Wesley, Sagartz, John E., Schriewer, Jill, Mark Buller, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722602/
https://www.ncbi.nlm.nih.gov/pubmed/22381921
http://dx.doi.org/10.1016/j.antiviral.2012.02.005
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author Parker, Scott
Chen, Nanhai G.
Foster, Scott
Hartzler, Hollyce
Hembrador, Ed
Hruby, Dennis
Jordan, Robert
Lanier, Randall
Painter, George
Painter, Wesley
Sagartz, John E.
Schriewer, Jill
Mark Buller, R.
author_facet Parker, Scott
Chen, Nanhai G.
Foster, Scott
Hartzler, Hollyce
Hembrador, Ed
Hruby, Dennis
Jordan, Robert
Lanier, Randall
Painter, George
Painter, Wesley
Sagartz, John E.
Schriewer, Jill
Mark Buller, R.
author_sort Parker, Scott
collection PubMed
description The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2–3 post infection – thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals.
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spelling pubmed-37226022013-07-25 Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox Parker, Scott Chen, Nanhai G. Foster, Scott Hartzler, Hollyce Hembrador, Ed Hruby, Dennis Jordan, Robert Lanier, Randall Painter, George Painter, Wesley Sagartz, John E. Schriewer, Jill Mark Buller, R. Antiviral Res Article The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2–3 post infection – thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Elsevier B.V. 2012-04 2012-02-18 /pmc/articles/PMC3722602/ /pubmed/22381921 http://dx.doi.org/10.1016/j.antiviral.2012.02.005 Text en Copyright © 2012 Elsevier B.V. All rights reserved. Elsevier has created a Monkeypox Information Center (https://www.elsevier.com/connect/monkeypox-information-center) in response to the declared public health emergency of international concern, with free information in English on the monkeypox virus. The Monkeypox Information Center is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its monkeypox related research that is available on the Monkeypox Information Center - including this research content - immediately available in publicly funded repositories, with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the Monkeypox Information Center remains active.
spellingShingle Article
Parker, Scott
Chen, Nanhai G.
Foster, Scott
Hartzler, Hollyce
Hembrador, Ed
Hruby, Dennis
Jordan, Robert
Lanier, Randall
Painter, George
Painter, Wesley
Sagartz, John E.
Schriewer, Jill
Mark Buller, R.
Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title_full Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title_fullStr Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title_full_unstemmed Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title_short Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – An animal model of smallpox
title_sort evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox – an animal model of smallpox
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722602/
https://www.ncbi.nlm.nih.gov/pubmed/22381921
http://dx.doi.org/10.1016/j.antiviral.2012.02.005
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