FBA reveals guanylate kinase as a potential target for antiviral therapies against SARS-CoV-2

Bioinformatics. 2020 Dec 30;36(Suppl 2):i813-i821. doi: 10.1093/bioinformatics/btaa813.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • COVID-19* / drug therapy
  • Guanylate Kinases
  • Humans
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Guanylate Kinases

Supplementary concepts

  • COVID-19 drug treatment