@article{Renz2021c,
  author         = {Renz, Alina and Widerspick, Lina and Dr\"ager, Andreas},
  title          = {{Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms
    Guanylate Kinase as Robust Potential Antiviral Target}},
  journal        = {Genes},
  volume         = {12},
  number         = {6},
  article-number = {796},
  year           = {2021},
  month          = may,
  doi            = {10.3390/genes12060796},
  url            = {https://www.mdpi.com/2073-4425/12/6/796},
  pdf            = {https://www.mdpi.com/2073-4425/12/6/796/pdf},
  issn           = {2073-4425},
  keywords       = {SARS-CoV-2; COVID-19; flux balance analysis (FBA); genome-scale metabolic
    models; target identification; reaction knock-out; structural proteins; purine metabolism;
    pyrimidine metabolism; B.1.1.7; B.1.351; B.1.617; B.1.28; B.1.427/B.1.429},
  abstract       = {The current SARS-CoV-2 pandemic is still threatening humankind. Despite
    first successes in vaccine development and approval, no antiviral treatment is available
    for COVID-19 patients. The success is further tarnished by the emergence and spreading
    of mutation variants of SARS-CoV-2, for which some vaccines have lower efficacy. This
    highlights the urgent need for antiviral therapies even more. This article describes how
    the genome-scale metabolic model (GEM) of the host-virus interaction of human alveolar
    macrophages and SARS-CoV-2 was refined by incorporating the latest information about the
    virus's structural proteins and the mutant variants B.1.1.7, B.1.351, B.1.28, B.1.427/B.1.429,
    and B.1.617. We confirmed the initially identified guanylate kinase as a potential
    antiviral target with this refined model and identified further potential targets from
    the purine and pyrimidine metabolism. The model was further extended by incorporating the
    virus' lipid requirements. This opened new perspectives for potential antiviral targets in
    the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play
    a pivotal role in viral replication. The guanylate kinase is even a robust target in all
    investigated mutation variants currently spreading worldwide. These new insights can guide
    laboratory experiments for the validation of identified potential antiviral targets. Only
    the combination of vaccines and antiviral therapies will effectively defeat this ongoing
    pandemic.},
}