COVID-19奇怪地导致一些年轻人死亡，而这些年轻人没有体弱的病史，除了对肺部的影响，它甚至还可能直接损害其他器官。其复杂的机制导致失去了任何明显有效的药物，一些重症患者仍然每天死亡。常用的疾病机制和药物设计的鉴定方法往往耗时或具有还原主义特点。在这里，我们使用了一种新的整体系统生物学方法来预测其分子机制（体外）、与SARS的显著分子关系以及药物的再应用。我们利用其与SARS的相对系统发育相似性进行了分析。使用可获取的SARS组学数据和较少的COVID-19数据来解码机制及其重要关系，我们应用了Cytoscape分析仪、MCODE、STRING和DAVID工具来预测在拓扑地理上重要的分子、群集、蛋白质相互作用映射和功能分析。我们还应用了一种新的方法，利用Fischer精确检验对MCODE群集之间的两个感染之间的重要关系进行了鉴定。然后，我们使用PharmGKB和DrugBank构建并分析了一个药物-基因网络（使用dgidb检索）。一些共同鉴定的关键分子、生物过程和通路包括Kaposi肉瘤相关疱疹病毒感染、甲型流感和NOD样受体信号通路。此外，我们还鉴定了与SARS-CoV-2宿主反应有关的重要分子，包括FGA、BMP4、PRPF40A和IFI16。我们还根据药物-基因网络分析为鉴定的关键分子引入了七种新的再应用候选药物。因此，我们建议进一步在COVID-19中对我们新推荐的再应用药物进行体外和体内研究。© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.

COVID-19 strangely kills some youth with no history of physical weakness, and in addition to the lungs, it may even directly harm other organs. Its complex mechanism has led to the loss of any significantly effective drug, and some patients with severe forms still die daily. Common methods for identifying disease mechanisms and drug design are often time-consuming or reductionist. Here, we use a novel holistic systems biology approach to predict its molecular mechanisms (in vitro), significant molecular relations with SARS, and repurpose drugs.We have utilized its relative phylogenic similarity to SARS. Using the available omics data for SARS and the fewer data for COVID-19 to decode the mechanisms and their significant relations, We applied the Cytoscape analyzer, MCODE, STRING, and DAVID tools to predict the topographically crucial molecules, clusters, protein interaction mappings, and functional analysis. We also applied a novel approach to identify the significant relations between the two infections using the Fischer exact test for MCODE clusters. We then constructed and analyzed a drug-gene network using PharmGKB and DrugBank (retrieved using the dgidb).Some of the shared identified crucial molecules, BPs and pathways included Kaposi sarcoma-associated herpesvirus infection, Influenza A, and NOD-like receptor signaling pathways. Besides, our identified crucial molecules specific to host response against SARS-CoV-2 included FGA, BMP4, PRPF40A, and IFI16.We also introduced seven new repurposed candidate drugs based on the drug-gene network analysis for the identified crucial molecules. Therefore, we suggest that our newly recommended repurposed drugs be further investigated in Vitro and in Vivo against COVID-19.© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.