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10.1371/journal.pone.0257784

http://scihub22266oqcxt.onion/10.1371/journal.pone.0257784
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34582497!8478222!34582497
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suck abstract from ncbi


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pmid34582497      PLoS+One 2021 ; 16 (9): e0257784
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  • Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium #MMPMID34582497
  • Gupta RK; Nwachuku EL; Zusman BE; Jha RM; Puccio AM
  • PLoS One 2021[]; 16 (9): e0257784 PMID34582497show ga
  • Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel ;gene signature'-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.
  • |*COVID-19 Drug Treatment[MESH]
  • |Antiviral Agents/therapeutic use[MESH]
  • |Drug Evaluation, Preclinical/methods[MESH]
  • |Drug Repositioning/*methods[MESH]
  • |Epithelial Cells/drug effects[MESH]
  • |Epithelium/drug effects[MESH]
  • |Humans[MESH]
  • |Respiratory Mucosa/drug effects/metabolism/virology[MESH]
  • |Respiratory System/drug effects[MESH]


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