Abstract
MotivationThe 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.ResultsWe 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 implementationThe computational model is accessible at https://identifiers.org/biomodels.db/MODEL2003020001.
Highlights
We developed a genome-scale metabolic model (GEM) of a human macrophage infected with the Severe Acute Respiratory Syndrome (SARS)-CoV-2
The human alveolar macrophage biomass maintenance function is comprised of several macromolecules, including amino acids, deoxyribonucleic acid (DNA) and RNA nucleotides, components for the energy requirements and others, such as fatty acids or phospholipids
We presented a host-virus integrated GEM using the human alveolar macrophage model iAB-AMØ-1410 as host cells and SARS-CoV-2 as virus
Summary
In December 2019, an outbreak of pneumonia in Wuhan, Hubei province, in China, has aroused the interest of the international community by showing alarming similarities to the outbreaks caused by other b-coronaviruses (b-CoV) like the Severe Acute Respiratory Syndrome (SARS) virus (Huang et al, 2020; Hui et al, 2020).The febrile respiratory illness caused by the novel coronavirus (SARS-CoV-2) is thought to have spread as a zoonosis from the Huanan Seafood Wholesale Market, which was as a consequence shut down on January 1, 2020 to prevent further transmission events (Hui et al, 2020).On January 7, first isolation and subsequent deep-sequencing of SARS-CoV-2 from the human lower respiratory tract samples have made the genetic sequence of the virus available to the public by January 12, 2020, allowing for the identification of the virus as a Group 2B b-CoV (Huang et al, 2020; Hui et al, 2020). In December 2019, an outbreak of pneumonia in Wuhan, Hubei province, in China, has aroused the interest of the international community by showing alarming similarities to the outbreaks caused by other b-coronaviruses (b-CoV) like the Severe Acute Respiratory Syndrome (SARS) virus (Huang et al, 2020; Hui et al, 2020). The febrile respiratory illness caused by the novel coronavirus (SARS-CoV-2) is thought to have spread as a zoonosis from the Huanan Seafood Wholesale Market, which was as a consequence shut down on January 1, 2020 to prevent further transmission events (Hui et al, 2020). SARSCoV-2 has 82% sequence similarity with the SARS virus, which has caused an outbreak originating in China in 2002 (Hui et al, 2020; Zhang et al, 2020). The resemblance and the severe global health threat have initiated a swift and determined implementation of public health measures by the Chinese Authorities (Chen et al, 2020; Hui et al, 2020)
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