Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing.
BMC Med Genomics
; 14(1): 226, 2021 09 17.
Article
in English
| MEDLINE | ID: covidwho-1542114
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Drug Repositioning
/
Pandemics
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
/
Lung Diseases
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
BMC Med Genomics
Journal subject:
Genetics, Medical
Year:
2021
Document Type:
Article
Affiliation country:
S12920-021-01079-7
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