Renz2020 - GEM of Human alveolar macrophage with SARS-CoV-2

  public model
Model Identifier
MODEL2003020001
Short description
Background: The novel coronavirus (SARS-CoV-2) currently spreads worldwide, causing the disease COVID-19. The number of infections increases daily, without any approved antiviral therapy. The recently released viral nucleotide sequence enables the identification of therapeutic targets, e.g., by analyzing integrated human-virus metabolic models. Investigations of changed metabolic processes after virus infections and the effect of knock-outs on the host and the virus can reveal new potential targets. Results: We generated an integrated host-virus genome-scale metabolic model of human alveolar macrophages and SARS-CoV-2. Analyses of stoichiometric and metabolic changes between uninfected and infected host cells using flux balance analysis (FBA) highlighted the different requirements of host and virus. Conclusion: Consequently, alterations in the metabolism can have different effects on host and virus, leading to potential antiviral targets. One of these potential targets is guanylate kinase (GK1). In FBA analyses, the knock-out of the guanylate kinase decreased the growth of the virus to zero, while not affecting the host. As GK1 inhibitors are described in the literature, its potential therapeutic effect for SARS-CoV-2 infections needs to be verified in in-vitro experiments.
Format
COMBINE archive (0.1)
Related Publication
  • FBA reveals guanylate kinase as a potential target for antiviral therapies against SARS-CoV-2
  • Alina Renz, Lina Widerspick, Andreas Dräger
  • Bioinformatics , 12/ 2020 , Volume 36 , Issue Supplement_2 , pages: i813-i821 , Other Link (URL): https://doi.org/10.1093/bioinformatics/btaa813
  • Computational Systems Biology of Infections and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
  • Motivation The novel coronavirus (SARS-CoV-2) currently spreads worldwide, causing the disease COVID-19. The number of infections increases daily, without any approved antiviral therapy. The recently released viral nucleotide sequence enables the identification of therapeutic targets, e.g. by analyzing integrated human-virus metabolic models. Investigations of changed metabolic processes after virus infections and the effect of knock-outs on the host and the virus can reveal new potential targets. Results We generated an integrated host–virus genome-scale metabolic model of human alveolar macrophages and SARS-CoV-2. Analyses of stoichiometric and metabolic changes between uninfected and infected host cells using flux balance analysis (FBA) highlighted the different requirements of host and virus. Consequently, alterations in the metabolism can have different effects on host and virus, leading to potential antiviral targets. One of these potential targets is guanylate kinase (GK1). In FBA analyses, the knock-out of the GK1 decreased the growth of the virus to zero, while not affecting the host. As GK1 inhibitors are described in the literature, its potential therapeutic effect for SARS-CoV-2 infections needs to be verified in in-vitro experiments. Availability and implementation The computational model is accessible at https://identifiers.org/biomodels.db/MODEL2003020001.
Contributors
Submitter of the first revision: Andreas Dräger
Submitter of this revision: Andreas Dräger
Modellers: Rahuman Sheriff, Andreas Dräger

Metadata information

Curation status
Non-curated
Modelling approach(es)
constraint-based model
Tags
COVID-19

Connected external resources

Name Description Size Actions

Model files
iAB_AMO1410_SARS-CoV-2.omex OMEX Version 1 445.99 KB Preview | Download

Additional files
iAB_AMO1410_SARS-CoV-2.xml SBML L3V1 7.57 MB Preview | Download

  • Model originally submitted by : Andreas Dräger
  • Submitted: Mar 17, 2020 4:22:30 PM
  • Last Modified: Apr 29, 2021 4:07:17 PM
Revisions
  • Version: 9 public model Download this version
    • Submitted on: Apr 29, 2021 4:07:17 PM
    • Submitted by: Andreas Dräger
    • With comment: Refinement of the structural proteins in the viral biomass objective function based on new data.
  • Version: 8 public model Download this version
    • Submitted on: Mar 17, 2020 4:22:30 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Edited model metadata online.

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