| Autor: |
Ali Kishk, Maria Pires Pacheco, Thomas Sauter |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 24, Iss 11, Pp 103331- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2021.103331 |
| Popis: |
Summary: The 2019 coronavirus disease (COVID-19) became a worldwide pandemic with currently no approved effective antiviral drug. Flux balance analysis (FBA) is an efficient method to analyze metabolic networks. Here, FBA was applied on human lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reposition metabolic drugs and drug combinations against the virus replication within the host tissue. Making use of expression datasets of infected lung tissue, genome-scale COVID-19-specific metabolic models were reconstructed. Then, host-specific essential genes and gene pairs were determined through in silico knockouts that permit reducing the viral biomass production without affecting the host biomass. Key pathways that are associated with COVID-19 severity in lung tissue are related to oxidative stress, ferroptosis, and pyrimidine metabolism. By in silico screening of Food and Drug Administration (FDA)-approved drugs on the putative disease-specific essential genes and gene pairs, 85 drugs and 52 drug combinations were predicted as promising candidates for COVID-19 (https://github.com/sysbiolux/DCcov). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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