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首页> 外文期刊>IEEE/ACM transactions on computational biology and bioinformatics >Network-Based Analysis of Fatal Comorbidities of COVID-19 and Potential Therapeutics
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Network-Based Analysis of Fatal Comorbidities of COVID-19 and Potential Therapeutics

机译：基于网络的Covid-19和潜在治疗方法的致命致命性分析

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摘要

COVID-19 is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The case-fatality rate is significantly higher in older patients and those with diabetes, cancer or cardiovascular disorders. The human proteins, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and basigin (BSG), are involved in high-confidence host-pathogen interactions with SARS-CoV-2 proteins. We considered these three proteins as seed nodes and applied the random walk with restart method on the human interactome to construct a protein-protein interaction sub-network, which captures the effects of viral invasion. We found that 'Insulin resistance', 'AGE-RAGE signaling in diabetic complications' and 'adipocytokine signaling' were the common pathways associated with diabetes, cancer and cardiovascular disorders. The association of these critical pathways with aging and its related diseases explains the molecular basis of COVID-19 fatality. We further identified drugs that have effects on these proteins/pathways based on gene expression studies. We particularly focused on drugs that significantly downregulate ACE2 along with other critical proteins identified by the network-based approach. Among them, COL-3 had earlier shown activity against acute lung injury and acute respiratory distress, while entinostat and mocetinostat have been investigated for non-small-cell lung cancer. We propose that these drugs can be repurposed for COVID-19.
机译：Covid-19是由严重急性呼吸综合征冠状病毒2（SARS-COV-2）引起的高度传染性疾病。老年患者和患有糖尿病，癌症或心血管疾病的病症的病例率明显高。人蛋白，血管紧张素转化酶2（ACE2），跨膜蛋白酶丝氨酸丝氨酸2（TMPRSS2）和Basigin（BSG）涉及与SARS-COV-2蛋白的高置信宿主 - 病原体相互作用。我们将这三种蛋白质视为种子节点并用重启方法施加随机步行，以构建蛋白质 - 蛋白质相互作用子网络，其捕获病毒侵袭的影响。我们发现“胰岛素抵抗力”，“糖尿病并发症中的年龄愤怒信号传导”是与糖尿病，癌症和心血管障碍相关的常见途径。这些关键途径与老化的关联及其相关疾病解释了Covid-19致命的分子基础。我们进一步确定了基于基因表达研究对这些蛋白质/途径产生影响的药物。我们特别专注于药物显着下调ACE2以及基于网络方法所识别的其他关键蛋白质。其中，COL-3早些时候显示了针对急性肺损伤和急性呼吸窘迫的活性，而突出的患者和Mocetinostat已经针对非小细胞肺癌进行了研究。我们建议这些药物可以重新掌握Covid-19。

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