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Funder: Wellcome Trust, 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.

The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for over 500 thousand deaths in 216 countries across the world and is affecting over 10 million people. The absence of FDA approved drugs against the new SARS-CoV-2 virus has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and the SARS-CoV-2 virus to provide insight into the pathogenetic mechanism of the virus and to support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first of all, in its healthy state. We then demonstrate how the entry of the SARS-CoV-2 virus into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. We have completed a comparative analysis of our model and other previously generated cell type models and highlight 48 pathways and over 800 reactions hijacked by the virus for its replication and survival. We designed a new tool which predicts 15 unique reactions as drug targets from our models (the integrated human macrophage, human airway epithelial cells and the SARS-CoV2 virus) and provide a platform for future studies on viral entry inhibition and drug optimisation strategies.