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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach
Tamizhini Loganathan1, Srimathy Ramachandran1, Prakash Shankaran1
1School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur, India.
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.
Insights
This study identified host factors crucial for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Drug repurposing analysis revealed 27 potential COVID-19 treatments, including twelve with known antiviral activity.
Area of Science:
- Virology
- Computational Biology
- Pharmacology
Background:
- The COVID-19 pandemic necessitates rapid identification of effective therapeutic strategies.
- Drug repurposing offers a swift approach to discover potential treatments for SARS-CoV-2 infection by targeting viral and host factors.
Purpose of the Study:
- To identify host-derived pro-viral factors implicated in SARS-CoV-2 infection.
- To conduct drug repurposing analysis to find existing drugs that can counteract these pro-viral factors.
Main Methods:
- Utilized a host transcriptome-based drug repurposing strategy using gene expression data.
- Analyzed pro-viral factors identified in SARS-CoV-2 infection models.
- Employed DrugBank and Connectivity Map (CMap) via the CLUE web tool for drug repurposing.
Main Results:
- Identified upregulated pro-viral host factors including TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3.
- Discovered 27 drugs capable of reversing pro-viral factor expression, with twelve exhibiting reported antiviral activity.
- Highlighted PTGS2 inhibition as a therapeutic strategy, suggesting six approved PTGS2 inhibitors for COVID-19 treatment.
Conclusions:
- Computational drug repurposing can propose candidate therapeutics for COVID-19.
- Further experimental validation is essential to confirm the efficacy of identified drugs against SARS-CoV-2.
