We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE.
Results: The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.
In summary, we have used publicly available human host gene expression profiles in early infection conditions of SARS-CoV-2 and other respiratory infection viruses and identified the important host factors in SARS-CoV-2 infection. Considering the consistent expression signature and literature evidence, we could identify 31 upregulated host factors, and out of them, eight are pro-viral factors in SARS-CoV-2 infection. The study is an effort to identify repurposed drugs for the treatment of SARS-CoV-2 infection, considering the pro-viral host factors. The connectivity map based repurposing proposed twelve compounds with evident antiviral activity from the literature survey. Apart from that, we could propose that inhibition of PTGS2 can be a potential therapeutic strategy for viral infection, and the proposed six approved PTGS2 inhibitor drugs can be repurposed for the treatment of SARS-CoV-2 infection. The study is based on the presently available dataset in public domain databases and may fluctuate based on the sample selection in the analysis. Therefore, we have considered strict criteria of consistency in expression patterns and evidence from the literature in the selection of host factors for repurposing studies. The rapid therapeutic recommendations from this computational approach can be repeated as more RNA-Seq datasets become available and could be done on protein-level and need to be validated by wet-lab experiments and clinical trials.
Reference & source information: https://peerj.com/
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