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.
A novel logical model of COVID-19 intracellular infection to support therapies development / Piretto, E.; Selvaggio, G.; Bragantini, D.; Domenici, E.; Marchetti, L.. - In: PLOS COMPUTATIONAL BIOLOGY. - ISSN 1553-7358. - 18:8(2022), pp. e101044301-e101044321. [10.1371/journal.pcbi.1010443]
A novel logical model of COVID-19 intracellular infection to support therapies development
Piretto E.Primo
;Domenici E.Penultimo
;Marchetti L.
Ultimo
2022-01-01
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.File | Dimensione | Formato | |
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