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

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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
SBML (L3V1)
Related Publication
  • FBA reveals guanylate kinase as potential target for antiviral therapies against coronavirus SARS-CoV-2
  • Alina Renz, Lina Widerspick, Andreas Dräger
  • Technical Report , 2/ 2020 , Other Link (URL): https://csbnc.informatik.uni-tuebingen.de/s/tbWGQq8iwSfHLCR
  • Computational Systems Biology of Infection and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
  • 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.
Contributors
Rahuman Sheriff, Andreas Dräger

Metadata information


Curation status
Non-curated

Modelling approach(es)

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Model files

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

  • Model originally submitted by : Andreas Dräger
  • Submitted: 17-Mar-2020 16:22:30
  • Last Modified: 17-Mar-2020 16:22:30
Revisions
  • Version: 8 public model Download this version
    • Submitted on: 17-Mar-2020 16:22:30
    • Submitted by: Rahuman Sheriff
    • With comment: Edited model metadata online.
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