Warwick scientists design model to predict cellular drug targets against COVID-19

November 25, 2020

A computational model of a human lung cell has been used to understand how SARS-CoV-2 draws on human host cell metabolism to reproduce by researchers at the University of Warwick. This study helps understand how the virus uses the host to survive, and enable drug predictions for treating the virus to be made.

Viruses rely on their host to survive, a crucial step of lifecycle is the synthesis of the virus particles within the host cell, therefore understanding this process is key to finding ways to prevent the virus from surviving.

Using a computer model of a human lung cell metabolism, scientists from the School of Life Sciences at the University of Warwick have captured the stoichiometric amino and nucleic acid requirements of SARS-CoV-2, the virus that causes Covid-19. Publishing their results in the paper, 'Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network', in the journal Life Science Alliance.

Their model has identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction, highlighting reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. In fact, researchers found that only few of these metabolic perturbations are able to selectively inhibit virus reproduction.

Researchers have also noted that 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.

Professor Orkun Soyer, from the School of Life Sciences at the University of Warwick comments:

"We have created a stoichiometric biomass function for the COVID-19-causing SARS-CoV-2 virus and incorporated this into a human lung cell genome scale metabolic model.

"We then predicted reaction perturbations that can inhibit SARS-CoV-2 reproduction in general or selectively, without inhibiting the host metabolic maintenance. The predicted reactions primarily fall onto glycolysis and oxidative phosphorylation pathways, and their connections to amino acid biosynthesis pathways."

Dr Hadrien Delattre, from the School of Life Sciences at the University of Warwick adds:

"Together, these results highlight the possibility of targeting host metabolism for inhibition of SARS-CoV-2 reproduction in human cells in general and in human lung cells specifically.

He added, "More research needs to be carried out to explore SARS-CoV-2 infected cells and their metabolism, however the model developed here by the researchers can be used as a starting point for testing out specific drug predictions".
-end-
25 NOVEMBER 2020

NOTES TO EDITORS

High-res images available at: https://warwick.ac.uk/services/communications/medialibrary/images/november_2020/delaterre_jpeg.jpg

Caption: Schematic representation of the integrated host-virus metabolic modelling approach used in the article. The biomass composition of SARS-CoV-2 is estimated based on genomic and structural informations and then embedded in the metabolic network model of the host cell. This model is then used to predict the metabolic fluxes supporting virus production and effects of perturbations.

Credit: University of Warwick

Paper available to view at: https://www.life-science-alliance.org/content/4/1/e202000869

For further information please contact:

Alice Scott
Media Relations Manager - Science
University of Warwick
Tel: +44 (0) 7920 531 221
E-mail: alice.j.scott@warwick.ac.uk

University of Warwick

Related Metabolism Articles from Brightsurf:

Early trauma influences metabolism across generations
A study by the Brain Research Institute at UZH reveals that early trauma leads to changes in blood metabolites - similarly in mice and humans.

Cannabinoids decrease the metabolism of glucose in the brain
What happens when THC acts on the glial cells named astrocytes ?

New role of arginine metabolism in plant morphogenesis identified
A research team led by ExCELLS/NIBB found that arginine metabolism has a vital role in regulating gametophore shoot formation in the moss Physcomitrium patens.

Watching changes in plant metabolism -- live
Almost all life on Earth, e.g. our food and health, depend on metabolism in plants.

redHUMAN: Deciphering links between genes and metabolism
Scientists at EPFL have developed a new method that simplifies the processing of genetic-metabolic data by picking up changes in metabolism, a hallmark of numerous diseases like cancer and Alzheimer's.

Lipid metabolism controls brain development
A lipid metabolism enzyme controls brain stem cell activity and lifelong brain development.

Inhibition of sphingolipid metabolism and neurodegenerative diseases
Disrupting the production of a class of lipids known as sphingolipids in neurons improved symptoms of neurodegeneration and increased survival in a mouse model.

Viruses don't have a metabolism; but some have the building blocks for one
'Giant viruses' are many times larger than typical viruses and have more complex genomes.

New metabolism discovered in bacteria
Microbiologists at Goethe University Frankfurt have discovered how the bacterium Acetobacterium woodii uses hydrogen in a kind of cycle to conserve energy.

Protein controls fat metabolism
A protein in the cell envelope influences the rate of fatty acid uptake in cells.

Read More: Metabolism News and Metabolism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.