Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. Methods 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.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, host transcriptome, 【초록키워드】 Treatment, Coronavirus disease 2019, coronavirus, pandemic, Gene Expression, SARS-COV-2 infection, drug, Factors, anti-viral activity, DrugBank, inhibitor, expression, therapeutic strategy, Evidence, Analysis, early infection, cell type, World Health Organization, acute respiratory syndrome, Factor, subject, PTGS2, CXCL2, connectivity, TYMP, Ifi44, CXCL3, XAF1, Host, approach, effective, expression profile, Result, caused, reported, required, approved, adopted, upregulated, gene product, Map, CFB, respiratory infection viruses, 【제목키워드】 Meta-analysis, approach,