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Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network
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Delattre, Hadrien, Sasidharan, Kalesh and Soyer, Orkun S. (2021) Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network. Life Science Alliance, 4 (1). e202000869. doi:10.26508/lsa.202000869 ISSN 2575-1077.
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WRAP-Inhibiting-reproduction-SARS-CoV-2-lung-cell-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1520Kb) | Preview |
Official URL: https://doi.org/10.26508/lsa.202000869
Abstract
Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction. Our results highlight reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. By incorporating host cellular maintenance into the model based on available protein expression data from human lung cells, we find that only few of these metabolic perturbations are able to selectively inhibit virus reproduction. Some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA interference techniques. In summary, the developed computational approach offers a platform for rapid, experimentally testable generation of drug predictions against existing and emerging viruses based on their biomass requirements.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RA Public aspects of medicine R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | COVID-19 (Disease) , SARS (Disease) , SARS (Disease) -- Epidemiology, Lungs -- Cytology, Cells -- Motility, Proteomics | |||||||||
| Journal or Publication Title: | Life Science Alliance | |||||||||
| Publisher: | Life Science Alliance, LLC | |||||||||
| ISSN: | 2575-1077 | |||||||||
| Official Date: | January 2021 | |||||||||
| Dates: |
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| Volume: | 4 | |||||||||
| Number: | 1 | |||||||||
| Article Number: | e202000869 | |||||||||
| DOI: | 10.26508/lsa.202000869 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 20 January 2021 | |||||||||
| Date of first compliant Open Access: | 20 January 2021 | |||||||||
| RIOXX Funder/Project Grant: |
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