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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

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Official URL: https://doi.org/10.26508/lsa.202000869

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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
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine
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:
DateEvent
January 2021Published
24 November 2020Available
11 November 2020Accepted
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
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/T010150/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/S506783/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
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