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基于新冠肺炎合并症通路串扰预测靶点和药物:迈向个性化新冠肺炎管理

Predicting COVID-19-Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management.

作者信息

Barh Debmalya, Aljabali Alaa A, Tambuwala Murtaza M, Tiwari Sandeep, Serrano-Aroca Ángel, Alzahrani Khalid J, Silva Andrade Bruno, Azevedo Vasco, Ganguly Nirmal Kumar, Lundstrom Kenneth

机构信息

Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, India.

Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.

出版信息

Biomedicines. 2021 May 17;9(5):556. doi: 10.3390/biomedicines9050556.

Abstract

It is well established that pre-existing comorbid conditions such as hypertension, diabetes, obesity, cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), cancers, and chronic obstructive pulmonary disease (COPD) are associated with increased severity and fatality of COVID-19. The increased death from COVID-19 is due to the unavailability of a gold standard therapeutic and, more importantly, the lack of understanding of how the comorbid conditions and COVID-19 interact at the molecular level, so that personalized management strategies can be adopted. Here, using multi-omics data sets and bioinformatics strategy, we identified the pathway crosstalk between COVID-19 and diabetes, hypertension, CVDs, CKDs, and cancers. Further, shared pathways and hub gene-based targets for COVID-19 and its associated specific and combination of comorbid conditions are also predicted towards developing personalized management strategies. The approved drugs for most of these identified targets are also provided towards drug repurposing. Literature supports the involvement of our identified shared pathways in pathogenesis of COVID-19 and development of the specific comorbid condition of interest. Similarly, shared pathways- and hub gene-based targets are also found to have potential implementations in managing COVID-19 patients. However, the identified targets and drugs need further careful evaluation for their repurposing towards personalized treatment of COVID-19 cases having pre-existing specific comorbid conditions we have considered in this analysis. The method applied here may also be helpful in identifying common pathway components and targets in other disease-disease interactions too.

摘要

众所周知,高血压、糖尿病、肥胖症、心血管疾病(CVDs)、慢性肾脏病(CKDs)、癌症和慢性阻塞性肺疾病(COPD)等预先存在的合并症与COVID-19的严重程度增加和死亡率升高有关。COVID-19导致的死亡人数增加是由于缺乏金标准治疗方法,更重要的是,缺乏对合并症与COVID-19在分子水平上如何相互作用的了解,因此无法采用个性化管理策略。在此,我们使用多组学数据集和生物信息学策略,确定了COVID-19与糖尿病、高血压、心血管疾病、慢性肾脏病和癌症之间的通路串扰。此外,还预测了COVID-19及其相关特定合并症和合并症组合的共享通路和基于枢纽基因的靶点,以制定个性化管理策略。还提供了针对这些已确定靶点中大多数的获批药物,用于药物再利用。文献支持我们确定的共享通路参与了COVID-19的发病机制以及相关特定合并症的发展。同样,基于共享通路和枢纽基因的靶点在管理COVID-19患者方面也具有潜在应用。然而,对于我们在本分析中考虑的患有预先存在特定合并症的COVID-19病例,所确定的靶点和药物在用于个性化治疗时需要进一步仔细评估。这里应用的方法可能也有助于识别其他疾病-疾病相互作用中的共同通路成分和靶点。

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