METHODS: We retrieved the omics data on respiratory cells infected with HCoV-229E and SARS-CoV-2, constructed PPIN and GRN, and detected clusters and motifs. Using a drug-gene interaction network, we determined the similarities and disparities of mechanisms behind their host response and drug-repurposed.
RESULTS: CXCL1, KLHL21, SMAD3, HIF1A, and STAT1 were the shared DEGs between both viruses\' protein-protein interaction network (PPIN) and gene regulatory network (GRN). The NPM1 was a specific critical node for HCoV-229E and was a Hub-Bottleneck shared between PPI and GRN in HCoV-229E. The HLA-F, ADCY5, TRIM14, RPF1, and FGA were the seed proteins in subnetworks of the SARS-CoV-2 PPI network, and HSPA1A and RPL26 proteins were the seed in subnetworks of the PPI network of HCOV-229E. TRIM14, STAT2, and HLA-F played the same role for SARS-CoV-2. Top enriched KEGG pathways included cell cycle and proteasome in HCoV-229E and RIG-I-like receptor, Chemokine, Cytokine-cytokine, NOD-like receptor, and TNF signaling pathways in SARS-CoV-2. We suggest some candidate medications for COVID-19 patient lungs, including Noscapine, Isoetharine mesylate, Cycloserine, Ethamsylate, Cetylpyridinium, Tretinoin, Ixazomib, Vorinostat, Venetoclax, Vorinostat, Ixazomib, Venetoclax, and epoetin alfa for further in-vitro and in-vivo investigations.
CONCLUSIONS: We suggested CXCL1, KLHL21, SMAD3, HIF1A, and STAT1, ADCY5, TRIM14, RPF1, and FGA, STAT2, and HLA-F as critical genes and Cetylpyridinium, Cycloserine, Noscapine, Ethamsylate, Epoetin alfa, Isoetharine mesylate, Ribavirin, and Tretinoin drugs to study further their importance in treating COVID-19 lung complications.
方法:我们检索了感染HCoV-229E和SARS-CoV-2的呼吸道细胞的组学数据,构建了PPIN和GRN,并检测到簇和主题。使用药物-基因相互作用网络,我们确定了其宿主反应和药物再利用背后机制的相似性和差异性.
结果:CXCL1,KLHL21,SMAD3,HIF1A,和STAT1是两种病毒蛋白质-蛋白质相互作用网络(PPIN)和基因调控网络(GRN)之间的共享DEG。NPM1是HCoV-229E的特定关键节点,并且是HCoV-229E中PPI和GRN之间共享的集线器瓶颈。HLA-F,ADCY5,TRIM14,RPF1和FGA是SARS-CoV-2PPI网络子网络中的种子蛋白,HSPA1A和RPL26蛋白是HCOV-229EPPI网络子网络中的种子。TRIM14,STAT2和HLA-F在SARS-CoV-2中起相同的作用。最富集的KEGG途径包括HCoV-229E和RIG-I样受体中的细胞周期和蛋白酶体,趋化因子,细胞因子-细胞因子,NOD样受体,SARS-CoV-2中的TNF信号通路。我们建议一些COVID-19患者肺部的候选药物,包括Noccapine,甲磺酸异丙嗪,环丝氨酸,Ethamsylate,十六烷基吡啶,维甲酸,Ixazomib,伏立诺他,维奈托克,伏立诺他,Ixazomib,维奈托克,和epoetinalfa用于进一步的体外和体内研究。
结论:我们建议CXCL1、KLHL21、SMAD3、HIF1A、和STAT1、ADCY5、TRIM14、RPF1和FGA,STAT2和HLA-F作为关键基因和十六烷基吡啶,环丝氨酸,Noccapine,Ethamsylate,依泊汀阿尔法,甲磺酸异丙嗪,利巴韦林,和维甲酸药物进一步研究它们在治疗COVID-19肺部并发症中的重要性。