Predicting COVID-19-Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management.
Predicting COVID-19-Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management.
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DOI：
10.3390/biomedicines9050556
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发表时间：
2021-05-17
期刊：
影响因子：
4.7
通讯作者：
Lundstrom K
中科院分区：
文献类型：
--
作者：
Barh D;Aljabali AA;Tambuwala MM;Tiwari S;Serrano-Aroca Á;Alzahrani KJ;Silva Andrade B;Azevedo V;Ganguly NK;Lundstrom K
众所周知，高血压、糖尿病、肥胖、心血管疾病 (CVD)、慢性肾病 (CKD)、癌症和慢性阻塞性肺病 (COPD) 等原有合并症与 COVID-19 的严重程度和死亡率增加有关。 COVID-19 死亡人数的增加是由于缺乏金标准治疗方法，更重要的是，缺乏对共病和 COVID-19 在分子水平上如何相互作用的了解，因此无法采取个性化的管理策略。在这里，我们利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、CVD、CKD 和癌症之间的通路串扰。此外，还预测了针对 COVID-19 及其相关特定疾病和合并症组合的共享途径和基于中心基因的目标，以制定个性化管理策略。针对大多数已确定目标的批准药物也可用于药物再利用。文献支持我们确定的共同途径参与了 COVID-19 的发病机制和感兴趣的特定合并症的发展。同样，基于共享途径和中心基因的目标也被发现在管理 COVID-19 患者方面具有潜在的实施意义。然而，确定的靶标和药物需要进一步仔细评估，以重新用于对具有我们在本分析中考虑的预先存在的特定合并症的 COVID-19 病例的个性化治疗。这里应用的方法也可能有助于识别其他疾病与疾病相互作用中的常见途径成分和靶点。
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.
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影响因子：
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