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Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bannerman, Bridget P  ORCID logo  https://orcid.org/0000-0002-5746-8283
Blundell, Tom L 
Moreno, Pablo 

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.

Description

Keywords

COVID-19, Computational Biology, Drug Development, Drug Evaluation, Preclinical, Humans, Models, Biological, Pandemics, SARS-CoV-2, COVID-19 Drug Treatment

Journal Title

Life Sci Alliance

Conference Name

Journal ISSN

2575-1077
2575-1077

Volume Title

4

Publisher

Life Science Alliance, LLC
Sponsorship
Wellcome Trust (107032/B/15/Z)