Abstract：
Coronavirus disease 2019 (COVID-19) is still an active global public health issue. Although vaccines and therapeutic options are available, some patients experience severe conditions and need critical care support. Hence, identifying key genes or proteins involved in immune-related severe COVID-19 is necessary to find or develop the targeted therapies. This study proposed a novel construction of an immune-related protein interaction network (IPIN) in severe cases with the use of a network diffusion technique on a human interactome network and transcriptomic data. Enrichment analysis revealed that the IPIN was mainly associated with antiviral, innate immune, apoptosis, cell division, and cell cycle regulation signaling pathways. Twenty-three proteins were identified as key proteins to find associated drugs. Finally, poly (I:C), mitomycin C, decitabine, gemcitabine, hydroxyurea, tamoxifen, and curcumin were the potential drugs interacting with the key proteins to heal severe COVID-19. In conclusion, IPIN can be a good representative network for the immune system that integrates the protein interaction network and transcriptomic data. Thus, the key proteins and target drugs in IPIN help to find a new treatment with the use of existing drugs to treat the disease apart from vaccination and conventional antiviral therapy.
摘要：
2019年冠状病毒病（COVID-19）仍然是一个活跃的全球公共卫生问题。尽管有疫苗和治疗选择，一些患者经历了严重的情况，需要重症监护支持。因此，识别与免疫相关的重症COVID-19相关的关键基因或蛋白质对于寻找或开发靶向治疗是必要的。这项研究提出了在严重情况下使用网络扩散技术对人类相互作用组网络和转录组数据进行免疫相关蛋白质相互作用网络（IPIN）的新构建。富集分析显示IPIN主要与抗病毒有关,先天免疫,凋亡，细胞分裂,和细胞周期调控信号通路。23种蛋白质被鉴定为寻找相关药物的关键蛋白质。最后,聚（I：C），丝裂霉素C,地西他滨,吉西他滨,羟基脲,他莫昔芬,姜黄素是与治疗严重COVID-19的关键蛋白相互作用的潜在药物。总之,IPIN可以是整合蛋白质相互作用网络和转录组数据的免疫系统的良好代表性网络。因此，IPIN中的关键蛋白和目标药物有助于寻找新的治疗方法，除了疫苗接种和常规抗病毒治疗外，使用现有药物治疗该疾病。
