Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host–virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on liver metabolism was investigated using integrated GEMs of human hepatocytes and SARS-CoV-2. They were generated for uninfected and infected hepatocytes using transcriptome data. Reporter metabolite analysis resulted in significant transcriptional changes around several metabolites involved in xenobiotics, drugs, arachidonic acid, and leukotriene metabolisms due to SARS-CoV-2 infection. Flux balance analysis and minimization of metabolic adjustment approaches unraveled possible virus-induced hepatocellular reprogramming in fatty acid, glycerophospholipid, sphingolipid cholesterol, and folate metabolisms, bile acid biosynthesis, and carnitine shuttle among others. Reaction knockout analysis provided critical reactions in glycolysis, oxidative phosphorylation, purine metabolism, and reactive oxygen species detoxification subsystems. Computational analysis also showed that administration of dopamine, glucosamine, D -xylose, cysteine, and ( R )-3-hydroxybutanoate contributes to alleviating viral infection. In essence, the reconstructed host–virus GEM helps us understand metabolic programming and develop therapeutic strategies to battle SARS-CoV-2.
Source: ACS Omega
Authors: Mustafa Sertbas, Kutlu O. Ulgen
Institution: Boğaziçi University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funder: Boğaziçi Üniversitesi
Award: G4777108300
OpenAlex ID: W4393095389