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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.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010443","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T13:47:25Z","timestamp":1661780845000},"page":"e1010443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel logical model of COVID-19 intracellular infection to support therapies development"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1609-7332","authenticated-orcid":true,"given":"Elena","family":"Piretto","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8911-7288","authenticated-orcid":true,"given":"Gianluca","family":"Selvaggio","sequence":"additional","affiliation":[]},{"given":"Damiano","family":"Bragantini","sequence":"additional","affiliation":[]},{"given":"Enrico","family":"Domenici","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-7705","authenticated-orcid":true,"given":"Luca","family":"Marchetti","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"pcbi.1010443.ref001","first-page":"262","article-title":"The chronology of the 2002\u20132003 SARS mini pandemic.","author":"JD Cherry","year":"2004"},{"key":"pcbi.1010443.ref002","first-page":"139","article-title":"Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus","author":"A Banerjee","year":"2019"},{"key":"pcbi.1010443.ref003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.onehlt.2016.12.001","article-title":"MERS-coronavirus: From discovery to intervention","volume":"3","author":"W Widagdo","year":"2017","journal-title":"One Heal"},{"key":"pcbi.1010443.ref004","doi-asserted-by":"crossref","first-page":"100694","DOI":"10.1016\/j.cegh.2020.100694","article-title":"Epidemiology and pathobiology of SARS-CoV-2 (COVID-19) in comparison with SARS, MERS: An updated overview of current knowledge and future perspectives","volume":"10","author":"B Ganesh","year":"2021","journal-title":"Clin Epidemiol Glob Heal"},{"key":"pcbi.1010443.ref005","first-page":"952","article-title":"SARS-CoV-2 variants and ending the COVID-19 pandemic","volume":"397","author":"AF Goddard","year":"2021"},{"key":"pcbi.1010443.ref006","article-title":"A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development","volume":"2","author":"C This","year":"2021"},{"key":"pcbi.1010443.ref007","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.it.2020.10.004","article-title":"Mechanisms of SARS-CoV-2 Transmission and Pathogenesis","volume":"41","author":"AG Harrison","year":"2020","journal-title":"Trends Immunol"},{"key":"pcbi.1010443.ref008","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.medj.2021.04.015","article-title":"COVID-19: The therapeutic landscape","volume":"2","author":"CI Paules","year":"2021","journal-title":"Med"},{"key":"pcbi.1010443.ref009","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"A Sette","year":"2021","journal-title":"Cell"},{"key":"pcbi.1010443.ref010","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"D Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"pcbi.1010443.ref011","article-title":"Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration. 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