ArticleJournal of the Royal Society, Interface2018
Integrated human-virus metabolic stoichiometric modelling predicts host-based antiviral targets against Chikungunya, Dengue and Zika viruses.
Article in Journal of the Royal Society, Interface, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed.
- Dynamic metabolic modelling of ATP allocation during viral infection.Journal of the Royal Society, Interface · 2026Article
- Family-wise resistance to infectious salmon anemia suggests that early systemic recognition protects against disease but not viral transcription.Frontiers in immunology · 2026Article
- Metabolic remodeling of microorganisms by mobile genetic elements alters mutualistic community composition.mSystems · 2025Article
- Metabolic modeling elucidates phenformin and atpenin A5 as broad-spectrum antiviral drugs against RNA viruses.Communications biology · 2025Article
- Metabolism-associated protein network constructing and host-directed anti-influenza drug repurposing.Briefings in bioinformatics · 2025Article
- Genome-scale model ofMicrobiology spectrum · 2024Article
- Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies.ACS omega · 2024Article
- Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic Targets.Infectious diseases & immunity · 2024Article
- Cell-specific genome-scale metabolic modeling of SARS-CoV-2-infected lung to identify antiviral enzymes.FEBS open bio · 2023Article
- Fuzzy optimization for identifying antiviral targets for treating SARS-CoV-2 infection in the heart.BMC bioinformatics · 2023Article
- Standards, dissemination, and best practices in systems biology.Current opinion in biotechnology · 2023Review
- New workflow predicts drug targets against SARS-CoV-2 via metabolic changes in infected cells.PLoS computational biology · 2023Article
- Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures.Metabolites · 2023Review
- Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity.Cell systems · 2022Article
- Human/SARS-CoV-2 genome-scale metabolic modeling to discover potential antiviral targets for COVID-19.Journal of the Taiwan Institute of Chemical Engineers · 2022Article
- Project-based learning course on metabolic network modelling in computational systems biology.PLoS computational biology · 2022Article
- Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication.Computational and structural biotechnology journal · 2022Article
- DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling.iScience · 2021Article
- Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19.Life science alliance · 2021Article
- Genome-scale metabolic modelling of SARS-CoV-2 in cancer cells reveals an increased shift to glycolytic energy production.FEBS letters · 2021Article
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4 authors.
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Abstract
Current and reoccurring viral epidemic outbreaks such as those caused by the Zika virus illustrate the need for rapid development of antivirals. Such development would be facilitated by computational approaches that can provide experimentally testable predictions for possible antiviral strategies. To this end, we focus here on the fact that viruses are directly dependent on their host metabolism for reproduction. We develop a stoichiometric, genome-scale metabolic model that integrates human macrophage cell metabolism with the biochemical demands arising from virus production and use it to determine the virus impact on host metabolism and vice versa. While this approach applies to any host-virus pair, we first apply it to currently epidemic viruses Chikungunya, Dengue and Zika in this study. We find that each of these viruses causes specific alterations in the host metabolic flux towards fulfilling their biochemical demands as predicted by their genome and capsid structure. Subsequent analysis of this integrated model allows us to predict a set of host reactions, which, when constrained, inhibit virus production. We show that this prediction recovers known targets of existing antiviral drugs, specifically those targeting nucleotide production, while highlighting a set of hitherto unexplored reactions involving both amino acid and nucleotide metabolic pathways, with either broad or virus-specific antiviral potential. Thus, this computational approach allows rapid generation of experimentally testable hypotheses for novel antiviral targets within a host.
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