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A novel logical model of COVID-19 intracellular infection to support therapies development

In this paper, a logical-based mathematical model of the cellular pathways involved in the COVID-19 infection has been developed to study various drug treatments (single or in combination), in different illness scenarios, providing insights into their mechanisms of action. Drug simulations suggest t...

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Autores principales: Piretto, Elena, Selvaggio, Gianluca, Bragantini, Damiano, Domenici, Enrico, Marchetti, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462742/
https://www.ncbi.nlm.nih.gov/pubmed/36037223
http://dx.doi.org/10.1371/journal.pcbi.1010443
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author Piretto, Elena
Selvaggio, Gianluca
Bragantini, Damiano
Domenici, Enrico
Marchetti, Luca
author_facet Piretto, Elena
Selvaggio, Gianluca
Bragantini, Damiano
Domenici, Enrico
Marchetti, Luca
author_sort Piretto, Elena
collection PubMed
description In this paper, a logical-based mathematical model of the cellular pathways involved in the COVID-19 infection has been developed to study various drug treatments (single or in combination), in different illness scenarios, providing insights into their mechanisms of action. Drug simulations suggest that the effects of single drugs are limited, or depending on the scenario counterproductive, whereas better results appear combining different treatments. Specifically, the combination of the anti-inflammatory Baricitinib and the anti-viral Remdesivir showed significant benefits while a stronger efficacy emerged from the triple combination of Baricitinib, Remdesivir, and the corticosteroid Dexamethasone. Together with a sensitivity analysis, we performed an analysis of the mechanisms of the drugs to reveal their impact on molecular pathways.
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spelling pubmed-94627422022-09-10 A novel logical model of COVID-19 intracellular infection to support therapies development Piretto, Elena Selvaggio, Gianluca Bragantini, Damiano Domenici, Enrico Marchetti, Luca PLoS Comput Biol Research Article In this paper, a logical-based mathematical model of the cellular pathways involved in the COVID-19 infection has been developed to study various drug treatments (single or in combination), in different illness scenarios, providing insights into their mechanisms of action. Drug simulations suggest that the effects of single drugs are limited, or depending on the scenario counterproductive, whereas better results appear combining different treatments. Specifically, the combination of the anti-inflammatory Baricitinib and the anti-viral Remdesivir showed significant benefits while a stronger efficacy emerged from the triple combination of Baricitinib, Remdesivir, and the corticosteroid Dexamethasone. Together with a sensitivity analysis, we performed an analysis of the mechanisms of the drugs to reveal their impact on molecular pathways. Public Library of Science 2022-08-29 /pmc/articles/PMC9462742/ /pubmed/36037223 http://dx.doi.org/10.1371/journal.pcbi.1010443 Text en © 2022 Piretto et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Piretto, Elena
Selvaggio, Gianluca
Bragantini, Damiano
Domenici, Enrico
Marchetti, Luca
A novel logical model of COVID-19 intracellular infection to support therapies development
title A novel logical model of COVID-19 intracellular infection to support therapies development
title_full A novel logical model of COVID-19 intracellular infection to support therapies development
title_fullStr A novel logical model of COVID-19 intracellular infection to support therapies development
title_full_unstemmed A novel logical model of COVID-19 intracellular infection to support therapies development
title_short A novel logical model of COVID-19 intracellular infection to support therapies development
title_sort novel logical model of covid-19 intracellular infection to support therapies development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462742/
https://www.ncbi.nlm.nih.gov/pubmed/36037223
http://dx.doi.org/10.1371/journal.pcbi.1010443
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