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

被引:17
作者
Barh, Debmalya [1 ,2 ]
Aljabali, Alaa A. [3 ]
Tambuwala, Murtaza M. [4 ]
Tiwari, Sandeep [2 ]
Serrano-Aroca, Angel [5 ]
Alzahrani, Khalid J. [6 ]
Silva Andrade, Bruno [7 ]
Azevedo, Vasco [2 ]
Ganguly, Nirmal Kumar [8 ,9 ,10 ]
Lundstrom, Kenneth [11 ]
机构
[1] Inst Integrat Omics & Appl Biotechnol IIOAB, Ctr Genom & Appl Gene Technol, Nonakuri 721172, Purba Medinipur, India
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Genet Ecol & Evolucao, BR-31270901 Belo Horizonte, MG, Brazil
[3] Yarmouk Univ, Dept Pharmaceut & Pharmaceut Technol, Fac Pharm, Irbid 21163, Jordan
[4] Ulster Univ, Sch Pharm & Pharmaceut Sci, Coleraine BT52 1SA, Londonderry, North Ireland
[5] Univ Catolica Valencia San Vicente Martir, Biomat & Bioengn Lab, Ctr Invest Traslac San Alberto Magno, Valencia 46001, Spain
[6] Taif Univ, Dept Clin Labs Sci, Coll Appl Med Sci, At Taif 21944, Saudi Arabia
[7] Univ Estadual Sudoeste Bahia UESB, Dept Ciencias Biol, Lab Bioinformat & Quim Computac, BR-45206190 Jequie, Brazil
[8] Jawaharlal Nehru Univ, Natl Inst Immunol, Aruna Asaf Ali Marg, New Delhi 110067, India
[9] Inst Liver & Biliary Sci, New Delhi 110070, India
[10] Translat Hlth Sci & Technol Inst, Policy Ctr Biomed Res, Faridabad 121001, India
[11] PanTherapeutics, CH-1095 Lutry, Switzerland
关键词
COVID-19; comorbidity; shared pathways; drug targets; personalized therapy; KAPPA-B PATHWAY; ENRICHMENT ANALYSIS; INHIBITORS; TNF; COMORBIDITY; INFECTION; IL-6; AGE;
D O I
10.3390/biomedicines9050556
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:16
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