A connectivity map-based drug repurposing study and integrative analysis of transcriptomic profiling of SARS-CoV-2 infection

Abstract

Aims

The recent outbreak of COVID-19 has become a global health concern. There are currently no effective treatment strategies and vaccines for the treatment or prevention of this fatal disease. The current study aims to determine promising treatment options for the COVID-19 through a computational drug repurposing approach.

Materials and methods

In this study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar cell line A549”. Next, the identified DEGs are used in the connectivity map (CMap) analysis to identify similarly acting therapeutic candidates. Furthermore, to interpret lists of DEGs, pathway enrichment and protein network analysis are performed. Genes are categorized into easily interpretable pathways based on their biological functions, and overrepresentation of each pathway is tested in comparison to what is expected randomly.

Key findings

The results suggest the effectiveness of lansoprazole, folic acid, sulfamonomethoxine, tolnaftate, diclofenamide, halcinonide, saquinavir, metronidazole, ebselen, lidocaine and benzocaine, histone deacetylase (HDAC) inhibitors, heat shock protein 90 (HSP90) inhibitors, and many other clinically approved drugs as potent drugs against COVID-19 outbreak.

Significance

Making new drugs remain a lengthy process, so the drug repurposing approach provides an insight into the therapeutics that might be helpful in this pandemic. In this study, pathway enrichment and protein network analysis are also performed, and the effectiveness of some drugs obtained from the CMap analysis has been investigated according to previous researches.

Highlights

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  Computational genomics analysis can accelerate drug discovery for the COVID-19.

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  SARS-CoV-2 transcriptome showed a chemokine-dominant hyperinflammatory response.

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  Robust IFN response with significant expression of ISGs pathway is seen in COVID-19.

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  The drug repurposing can be used as an alternative to de novo drug development.

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  Many approved drugs and investigational compounds showed antiviral properties.