A network biology approach to identify crucial host targets for COVID-19.

Autor: Barman RK; Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India; Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India., Mukhopadhyay A; Department of Computer Science and Engineering, University of Kalyani, Kalyani 741235, West Bengal, India., Maulik U; Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India., Das S; Division of Clinical Medicine, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India; ICMR-National Institute of Occupational Health, Ahmedabad 380016, India. Electronic address: dasss.niced@gov.in.
Jazyk: angličtina
Zdroj: Methods (San Diego, Calif.) [Methods] 2022 Jul; Vol. 203, pp. 108-115. Date of Electronic Publication: 2022 Mar 29.
DOI: 10.1016/j.ymeth.2022.03.016
Abstrakt: The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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