Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Daru. 2023 Dec;31(2):155-171. doi: 10.1007/s40199-023-00471-1. Epub 2023 Aug 19.
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.
COVID-19 会奇怪地杀死一些没有身体虚弱史的年轻人，而且除了肺部之外，它甚至可能直接损害其他器官。其复杂的机制导致任何具有显著疗效的药物都失效，一些重症患者仍每天死亡。识别疾病机制和药物设计的常用方法通常既耗时又过于简化。在这里，我们使用一种新颖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重新利用药物。
我们利用了它与 SARS 的相对系统发育相似性。利用 SARS 的可用组学数据和较少的 COVID-19 数据来解码机制及其重要关系，我们应用 Cytoscape 分析器、MCODE、STRING 和 DAVID 工具来预测拓扑上关键的分子、簇、蛋白质相互作用映射和功能分析。我们还应用了一种新方法来使用 MCODE 簇的 Fischer 精确检验识别两种感染之间的显著关系。然后，我们使用 PharmGKB 和 DrugBank（使用 dgidb 检索）构建和分析了一个药物-基因网络。
一些共享的关键分子、BP 和途径包括卡波济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，我们针对宿主对 SARS-CoV-2 的反应鉴定的关键分子还包括 FGA、BMP4、PRPF40A 和 IFI16。
我们还根据鉴定关键分子的药物-基因网络分析，引入了七种新的再利用候选药物。因此，我们建议进一步在体外和体内针对 COVID-19 对我们新推荐的再利用药物进行研究。
