ArticlePLoS computational biology2021
Genome Scale-Differential Flux Analysis reveals deregulation of lung cell metabolism on SARS-CoV-2 infection.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Integrative systems biology approaches for analyzing microbiome dysbiosis and species interactions.Briefings in bioinformatics · 2025Review
- Genome-scale metabolic modelling identifies reactions mediated by SNP-SNP interactions associated with yeast sporulation.NPJ systems biology and applications · 2025Article
- Metabolism-associated protein network constructing and host-directed anti-influenza drug repurposing.Briefings in bioinformatics · 2025Article
- Genome-scale models in human metabologenomics.Nature reviews. Genetics · 2025Review
- diel_models: a python package for systematic integration of day-night cycles into plant genome-scale metabolic models.Bioinformatics advances · 2025Article
- A diel multi-tissue genome-scale metabolic model of Vitis vinifera.PLoS computational biology · 2024Article
- Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic Targets.Infectious diseases & immunity · 2024Article
- Cell-specific genome-scale metabolic modeling of SARS-CoV-2-infected lung to identify antiviral enzymes.FEBS open bio · 2023Article
- Genome-scale metabolic models applied for human health and biopharmaceutical engineering.Quantitative biology (Beijing, China) · 2023Review
- Fuzzy optimization for identifying antiviral targets for treating SARS-CoV-2 infection in the heart.BMC bioinformatics · 2023Article
- New workflow predicts drug targets against SARS-CoV-2 via metabolic changes in infected cells.PLoS computational biology · 2023Article
- Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures.Metabolites · 2023Review
- Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19.iScience · 2022Article
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Integration of omics data to generate and analyse COVID-19 specific genome-scale metabolic models.Computers in biology and medicine · 2022Article
- A genome-scale metabolic model of Cupriavidus necator H16 integrated with TraDIS and transcriptomic data reveals metabolic insights for biotechnological applications.PLoS computational biology · 2022Article
- Human/SARS-CoV-2 genome-scale metabolic modeling to discover potential antiviral targets for COVID-19.Journal of the Taiwan Institute of Chemical Engineers · 2022Article
- A path-based analysis of infected cell line and COVID-19 patient transcriptome reveals novel potential targets and drugs against SARS-CoV-2.Research square · 2022Article
- Review
- The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy.Frontiers in pharmacology · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The COVID-19 pandemic is posing an unprecedented threat to the whole world. In this regard, it is absolutely imperative to understand the mechanism of metabolic reprogramming of host human cells by SARS-CoV-2. A better understanding of the metabolic alterations would aid in design of better therapeutics to deal with COVID-19 pandemic. We developed an integrated genome-scale metabolic model of normal human bronchial epithelial cells (NHBE) infected with SARS-CoV-2 using gene-expression and macromolecular make-up of the virus. The reconstructed model predicts growth rates of the virus in high agreement with the experimental measured values. Furthermore, we report a method for conducting genome-scale differential flux analysis (GS-DFA) in context-specific metabolic models. We apply the method to the context-specific model and identify severely affected metabolic modules predominantly comprising of lipid metabolism. We conduct an integrated analysis of the flux-altered reactions, host-virus protein-protein interaction network and phospho-proteomics data to understand the mechanism of flux alteration in host cells. We show that several enzymes driving the altered reactions inferred by our method to be directly interacting with viral proteins and also undergoing differential phosphorylation under diseased state. In case of SARS-CoV-2 infection, lipid metabolism particularly fatty acid oxidation, cholesterol biosynthesis and beta-oxidation cycle along with arachidonic acid metabolism are predicted to be most affected which confirms with clinical metabolomics studies. GS-DFA can be applied to existing repertoire of high-throughput proteomic or transcriptomic data in diseased condition to understand metabolic deregulation at the level of flux.
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