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Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China

A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 20...

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Autor principal: Kruse, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/
https://www.ncbi.nlm.nih.gov/pubmed/32117569
http://dx.doi.org/10.12688/f1000research.22211.2
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author Kruse, Robert L.
author_facet Kruse, Robert L.
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description A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).
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spelling pubmed-70297592020-02-27 Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China Kruse, Robert L. F1000Res Opinion Article A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s). F1000 Research Limited 2020-02-07 /pmc/articles/PMC7029759/ /pubmed/32117569 http://dx.doi.org/10.12688/f1000research.22211.2 Text en Copyright: © 2020 Kruse RL http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Opinion Article
Kruse, Robert L.
Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title_full Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title_fullStr Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title_full_unstemmed Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title_short Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
title_sort therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in wuhan, china
topic Opinion Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/
https://www.ncbi.nlm.nih.gov/pubmed/32117569
http://dx.doi.org/10.12688/f1000research.22211.2
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