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Authors:S T R Moolamalla et al.,  

Journal/ Pre-Print:BioRxiv 

Tags: Bioinformatics, Cell Biology 

Research Highlights   

  1. SARS‑CoV‑2 virus induces host-dependent dysregulation of glycolysis and mitochondrial metabolism. 

  1. SARS‑CoV‑2 virus triggers changes in amino acid metabolism, glutathione metabolism, polyamine synthesis, and lipid metabolism. 

  1. SARS‑CoV‑2 promotes metabolic changes associated with pro- and antiviral responses in nature.  

Summary  

Accumulating evidences highlight the role of metabolic reprogramming in promoting viral replication (Janelle S. AyresNature 2019). The study investigates the metabolic changes induced by SARS‑CoV‑2 virus in human respiratory cell lines, BALF and PBMC samples collected from patients. Analysis of differentially expressed genes (DEGs) show a downregulation of genes associated with TCA cycle and oxidative phosphorylation in cell lines along with upregulation of glycolytic enzymes genes, suggesting a shift in “Warburg effect” and defect in PI3K-Akt-mTOR-HIF1A axis in SARS-Cov-2. Additionally, genes of the pentose phosphate pathway and folate metabolism are downregulated in cell lines, suggesting a dysregulated Redox homeostasisGenes involved in fatty acid degradation and elongation were downregulated in cell lines along with upregulation of genes involved in sphingolipids synthesis. In addition, the study identifies the viral proteins which targets specific host metabolic pathways including MPro and ORF8 proteins and the potential transcription factors which are associated with metabolic changes. Collectively, the study provides comprehensive analysis of metabolic reprogramming induced by SARS-CoV2 to re-wire host antiviral immunity and suggest potential targets for therapeutic interventions.    

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Understand the virology and/or cell biology of SARS-CoV2/COVID19 

Study Type  

  • In silico study / bioinformatics study 

Strengths and limitations of the paper 

Novelty: The study provides a detailed transcriptomic analysis of host metabolic alterations in response to SARS-CoV-2 infection. 

Standing in the field: SARS-Cov-2 infection has been reported to induce host metabolic reprogramming in other studies (Singh et al., 2020(Ana Campos Codo et al2020). This study supports previous findings.  

Appropriate statistics: Yes 

Viral model used:SARS-CoV-2  

Translatability: Based on the dysregulation of some metabolic genes, some small molecules are proposed as potential antiviral therapy: PI3K inhibitors (Wortmannin and LY294002), polyamines synthesis (DFMO, Ribavirin, which is already in use for SARS-CoV-2), and targeting carbohydrate and amino acid metabolism, and redox homeostasis. 

Main limitations:  

  1. While the study compares metabolic changes in different cell lines and samples from patients, some metabolic changes were reported to be differentially altered across different cell lines or patient samples with a limited overlap in differentially expressed genes. Limited discussion was provided for such an observation. 

  1. Limited evidence reported for the infection status of patients (i.e moderate vs severe infections). It would be helpful to correlate the data of patient samples in relation to infection outcome, given that manipulation of host metabolic pathways is associated with SARS-CoV-2 pathogenesis (Keshav K. Singh et al, Cell Physiology, 2020). 

  1. A cohort of 3 patients is considered a relatively small size. Further studies with a larger sample size are necessary to investigate individual/population level variabilities and to confirm the findings. 

  1. This is also a purely bioinformatics analysis paper so there are no experiments to confirm the observations.