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.

中文翻译：

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集成的人类/SARS-CoV-2 代谢模型提出了针对 COVID-19 的新治疗策略。

由新型冠状病毒 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行目前在全球 219 个国家/地区造成超过 300 万人死亡，病例超过 1.4 亿。缺乏 FDA 批准的针对 SARS-CoV-2 的药物凸显了设计新药的迫切需要。我们开发了人类细胞和 SARS-CoV-2 的集成模型，以深入了解病毒的致病机制并支持当前的治疗策略。我们首先展示了人体细胞在其健康状态下的生长和一般维持所需的生化反应。然后，我们展示了 SARS-CoV-2 进入人体细胞如何引起生化和结构变化，从而导致细胞功能的变化或细胞死亡。一种新的计算方法，可以从我们的模型中预测 20 个独特的反应作为药物靶点，并为未来病毒进入抑制、免疫调节和药物优化策略的研究提供平台。该模型在 BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) 和软件工具中可用，实现计算方法的findCPcli可在 https://github.com/findCP/findCPcli 获得。