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Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing
BMC Medical Genomics ( IF 2.7 ) Pub Date : 2021-09-17 , DOI: 10.1186/s12920-021-01079-7
Asim Bikas Das 1
Affiliation  

Higher mortality of COVID-19 patients with lung disease is a formidable challenge for the health care system. Genetic association between COVID-19 and various lung disorders must be understood to comprehend the molecular basis of comorbidity and accelerate drug development. Lungs tissue-specific neighborhood network of human targets of SARS-CoV-2 was constructed. This network was integrated with lung diseases to build a disease–gene and disease-disease association network. Network-based toolset was used to identify the overlapping disease modules and drug targets. The functional protein modules were identified using community detection algorithms and biological processes, and pathway enrichment analysis. In total, 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases were found to be topologically overlapped with the COVID-19 module. Topological overlap with various lung disorders allows repurposing of drugs used for these disorders to hit the closely associated COVID-19 module. Further analysis showed that functional protein–protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. FDA-approved targets in the hijacked protein modules were identified and that can be hit by exiting drugs to rescue these modules from virus possession. Lung diseases are clustered with COVID-19 in the same network vicinity, indicating the potential threat for patients with respiratory diseases after SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19 and clinical evidence suggest that shared molecular features are the probable reason for comorbidity. Network-based drug repurposing approaches can be applied to improve the clinical conditions of COVID-19 patients.

中文翻译:

肺病网络揭示合并症对 SARS-CoV-2 感染的影响和药物再利用的机会

COVID-19 肺病患者死亡率较高是医疗保健系统面临的一项艰巨挑战。必须了解 COVID-19 与各种肺部疾病之间的遗传关联,以了解合并症的分子基础并加速药物开发。构建了 SARS-CoV-2 人类目标的肺组织特异性邻域网络。该网络与肺部疾病相结合,构建了疾病-基因和疾病-疾病关联网络。基于网络的工具集用于识别重叠的疾病模块和药物靶点。使用社区检测算法和生物过程以及通路富集分析来识别功能蛋白质模块。总共有 141 种肺部疾病与 SARS-CoV-2 目标的邻域网络​​有关,并且发现 59 种肺部疾病与 COVID-19 模块在拓扑上重叠。与各种肺部疾病的拓扑重叠允许重新利用用于这些疾病的药物来击中密切相关的 COVID-19 模块。进一步的分析表明,肺中的功能性蛋白质-蛋白质相互作用模块,基本上被 SARS-CoV-2 劫持,与几种肺部疾病有关。在被劫持的蛋白质模块中确定了 FDA 批准的目标,可以通过现有药物击中这些目标,以从病毒占有中拯救这些模块。肺部疾病与 COVID-19 聚集在同一网络附近,表明 SARS-CoV-2 感染后呼吸道疾病患者面临潜在威胁。肺部疾病与 COVID-19 的病理生物学相似性和临床证据表明,共同的分子特征是合并症的可能原因。基于网络的药物再利用方法可用于改善 COVID-19 患者的临床状况。
更新日期:2021-09-17
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