PDF(Pubmed)
Abstract：
OBJECTIVE: Identifying the molecular mechanisms behind SARS-CoV-2 disparities and similarities will help find new treatments. The present study determines networks\' shared and non-shared (specific) crucial elements in response to HCoV-229E and SARS-CoV-2 viruses to recommend candidate medications.
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.
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.
摘要：
目的：确定SARS-CoV-2差异和相似性背后的分子机制将有助于寻找新的治疗方法。本研究确定了响应HCoV-229E和SARS-CoV-2病毒的网络共享和非共享（特定）关键因素，以推荐候选药物。
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。
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。
