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

Authors: Alina Renz; Lina Widerspick; Andreas Dräger;

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

Abstract

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.

Keywords

SARS-CoV-2, Systems, Flux Balance Analysis, Genome-Scale Metabolic Model, COVID-19, Antiviral Agents, COVID-19 Drug Treatment, Coronavirus, Human Alveolar Macrophage, 2019-nCoV, Humans, Host-Virus Integration, Guanylate Kinases

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selected citations
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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