Article (Scientific journals)
DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling.
Kishk, Ali; Pires Pacheco, Maria Irene; Sauter, Thomas
2021In iScience, 24 (11), p. 103331
Peer reviewed
 

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Keywords :
Bioinformatics; Pharmaceutical science; Virology
Abstract :
[en] 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).
Research center :
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Kishk, Ali ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Pires Pacheco, Maria Irene ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Sauter, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
External co-authors :
no
Language :
English
Title :
DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling.
Publication date :
2021
Journal title :
iScience
ISSN :
2589-0042
Publisher :
Elsevier, Cambridge, United States - Massachusetts
Volume :
24
Issue :
11
Pages :
103331
Peer reviewed :
Peer reviewed
Commentary :
© 2021 The Authors.
Available on ORBilu :
since 11 November 2021

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