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Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing.
Das, Asim Bikas.
  • Das AB; Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India. asimbikas@nitw.ac.in.
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.
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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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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