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A novel logical model of COVID-19 intracellular infection to support therapies development.
Piretto, Elena; Selvaggio, Gianluca; Bragantini, Damiano; Domenici, Enrico; Marchetti, Luca.
  • Piretto E; European Institute of Oncology IRCCS, Milan, Italy.
  • Selvaggio G; Fondazione The Microsoft Research-University of Trento Centre for Computational and Systems Biology (COSBI), Rovereto, Trento, Italy.
  • Bragantini D; Infectious Diseases Unit, Pederzoli Hospital, Peschiera del Garda, Italy.
  • Domenici E; Fondazione The Microsoft Research-University of Trento Centre for Computational and Systems Biology (COSBI), Rovereto, Trento, Italy.
  • Marchetti L; Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Povo, Trento, Italy.
PLoS Comput Biol ; 18(8): e1010443, 2022 08.
Article in English | MEDLINE | ID: covidwho-2021468
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Limits: Humans Language: English Journal: PLoS Comput Biol Journal subject: Biology / Medical Informatics Year: 2022 Document Type: Article Affiliation country: Journal.pcbi.1010443

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Limits: Humans Language: English Journal: PLoS Comput Biol Journal subject: Biology / Medical Informatics Year: 2022 Document Type: Article Affiliation country: Journal.pcbi.1010443