Dataset Information

Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.

ABSTRACT: Tremendous progress has been made to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. However, effective therapeutic options are still rare. Drug repurposing and combination represent practical strategies to address this urgent unmet medical need. Viruses, including coronaviruses, are known to hijack host metabolism to facilitate viral proliferation, making targeting host metabolism a promising antiviral approach. Here, we describe an integrated analysis of 12 published in vitro and human patient gene expression datasets on SARS-CoV-2 infection using genome-scale metabolic modeling (GEM), revealing complicated host metabolism reprogramming during SARS-CoV-2 infection. We next applied the GEM-based metabolic transformation algorithm to predict anti-SARS-CoV-2 targets that counteract the virus-induced metabolic changes. We successfully validated these targets using published drug and genetic screen data and by performing an siRNA assay in Caco-2 cells. Further generating and analyzing RNA-sequencing data of remdesivir-treated Vero E6 cell samples, we predicted metabolic targets acting in combination with remdesivir, an approved anti-SARS-CoV-2 drug. Our study provides clinical data-supported candidate anti-SARS-CoV-2 targets for future evaluation, demonstrating host metabolism targeting as a promising antiviral strategy.

SUBMITTER: Cheng K

PROVIDER: S-EPMC8552660 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.

Cheng Kuoyuan K Martin-Sancho Laura L Pal Lipika R LR Pu Yuan Y Riva Laura L Yin Xin X Sinha Sanju S Nair Nishanth Ulhas NU Chanda Sumit K SK Ruppin Eytan E

Molecular systems biology 20211101 11

Tremendous progress has been made to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. However, effective therapeutic options are still rare. Drug repurposing and combination represent practical strategies to address this urgent unmet medical need. Viruses, including coronaviruses, are known to hijack host metabolism to facilitate viral proliferation, making targeting host metabolism a promising antiviral approach. Here, we describe an integrated analysis of 12 published in vitro and ...[more]

PMID: 34709707

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Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.

Publications

Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.

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