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Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19.
Eur J Pharmacol. 2020 Nov 15; 887:173594.EJ

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, more commonly COVID-19 has emerged as a world health pandemic. There are couples of treatment methods for COVID-19, however, well-established drugs and vaccines are urgently needed to treat the COVID-19. The new drug discovery is a tremendous challenge; repurposing of existing drugs could shorten the time and expense compared with de novo drug development. In this study, we aimed to decode molecular signatures and pathways of the host cells in response to SARS-CoV-2 and the rapid identification of repurposable drugs using bioinformatics and network biology strategies. We have analyzed available transcriptomic RNA-seq COVID-19 data to identify differentially expressed genes (DEGs). We detected 177 DEGs specific for COVID-19 where 122 were upregulated and 55 were downregulated compared to control (FDR<0.05 and logFC ≥ 1). The DEGs were significantly involved in the immune and inflammatory response. The pathway analysis revealed the DEGs were found in influenza A, measles, cytokine signaling in the immune system, interleukin-4, interleukin -13, interleukin -17 signaling, and TNF signaling pathways. Protein-protein interaction analysis showed 10 hub genes (BIRC3, ICAM1, IRAK2, MAP3K8, S100A8, SOCS3, STAT5A, TNF, TNFAIP3, TNIP1). The regulatory network analysis showed significant transcription factors (TFs) that target DEGs, namely FOXC1, GATA2, YY1, FOXL1, NFKB1. Finally, drug repositioning analysis was performed with these 10 hub genes and showed that in silico validated three drugs with molecular docking. The transcriptomics signatures, molecular pathways, and regulatory biomolecules shed light on candidate biomarkers and drug targets which have potential roles to manage COVID-19. ICAM1 and TNFAIP3 were the key hubs that have demonstrated good binding affinities with repurposed drug candidates. Dabrafenib, radicicol, and AT-7519 were the top-scored repurposed drugs that showed efficient docking results when they tested with hub genes. The identified drugs should be further evaluated in molecular level wet-lab experiments in prior to clinical studies in the treatment of COVID-19.

Authors+Show Affiliations

Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh.Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, Bangladesh; Department of Biochemistry and Biotechnology, School of Biomedical Science, Khwaja Yunus Ali University, Enayetpur, Sirajganj, Bangladesh. Electronic address: rezanur12@yahoo.com.Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.Department of Statistics, Begum Rokeya University, Rangpur, Bangladesh.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32971089

Citation

Islam, Tania, et al. "Integrative Transcriptomics Analysis of Lung Epithelial Cells and Identification of Repurposable Drug Candidates for COVID-19." European Journal of Pharmacology, vol. 887, 2020, p. 173594.
Islam T, Rahman MR, Aydin B, et al. Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19. Eur J Pharmacol. 2020;887:173594.
Islam, T., Rahman, M. R., Aydin, B., Beklen, H., Arga, K. Y., & Shahjaman, M. (2020). Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19. European Journal of Pharmacology, 887, 173594. https://doi.org/10.1016/j.ejphar.2020.173594
Islam T, et al. Integrative Transcriptomics Analysis of Lung Epithelial Cells and Identification of Repurposable Drug Candidates for COVID-19. Eur J Pharmacol. 2020 Nov 15;887:173594. PubMed PMID: 32971089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19. AU - Islam,Tania, AU - Rahman,Md Rezanur, AU - Aydin,Busra, AU - Beklen,Hande, AU - Arga,Kazim Yalcin, AU - Shahjaman,Md, Y1 - 2020/09/22/ PY - 2020/05/17/received PY - 2020/09/09/revised PY - 2020/09/21/accepted PY - 2020/9/25/pubmed PY - 2020/11/6/medline PY - 2020/9/24/entrez KW - COVID-19 KW - Drug repositioning, KW - SARS-CoV-2,transcriptomics SP - 173594 EP - 173594 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 887 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, more commonly COVID-19 has emerged as a world health pandemic. There are couples of treatment methods for COVID-19, however, well-established drugs and vaccines are urgently needed to treat the COVID-19. The new drug discovery is a tremendous challenge; repurposing of existing drugs could shorten the time and expense compared with de novo drug development. In this study, we aimed to decode molecular signatures and pathways of the host cells in response to SARS-CoV-2 and the rapid identification of repurposable drugs using bioinformatics and network biology strategies. We have analyzed available transcriptomic RNA-seq COVID-19 data to identify differentially expressed genes (DEGs). We detected 177 DEGs specific for COVID-19 where 122 were upregulated and 55 were downregulated compared to control (FDR<0.05 and logFC ≥ 1). The DEGs were significantly involved in the immune and inflammatory response. The pathway analysis revealed the DEGs were found in influenza A, measles, cytokine signaling in the immune system, interleukin-4, interleukin -13, interleukin -17 signaling, and TNF signaling pathways. Protein-protein interaction analysis showed 10 hub genes (BIRC3, ICAM1, IRAK2, MAP3K8, S100A8, SOCS3, STAT5A, TNF, TNFAIP3, TNIP1). The regulatory network analysis showed significant transcription factors (TFs) that target DEGs, namely FOXC1, GATA2, YY1, FOXL1, NFKB1. Finally, drug repositioning analysis was performed with these 10 hub genes and showed that in silico validated three drugs with molecular docking. The transcriptomics signatures, molecular pathways, and regulatory biomolecules shed light on candidate biomarkers and drug targets which have potential roles to manage COVID-19. ICAM1 and TNFAIP3 were the key hubs that have demonstrated good binding affinities with repurposed drug candidates. Dabrafenib, radicicol, and AT-7519 were the top-scored repurposed drugs that showed efficient docking results when they tested with hub genes. The identified drugs should be further evaluated in molecular level wet-lab experiments in prior to clinical studies in the treatment of COVID-19. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/32971089/Integrative_transcriptomics_analysis_of_lung_epithelial_cells_and_identification_of_repurposable_drug_candidates_for_COVID_19_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(20)30686-5 DB - PRIME DP - Unbound Medicine ER -