ABSTRACT
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-CoV-2 virus) and provide a platform for future studies on viral entry inhibition and drug optimisation strategies.