DTSEA: A network-based drug target set enrichment analysis method for drug repurposing against COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic is still wreaking havoc worldwide. Therefore, the urgent need for efficient treatments pushes researchers and clinicians into screening effective drugs. Drug repurposing may be a promising and time-saving strategy to identify potential drugs against this disease. Here, we developed a novel computational approach, named Drug Target Set Enrichment Analysis (DTSEA), to identify potent drugs against COVID-19. DTSEA first mapped the disease-related genes into a gene functional interaction network, and then it used a network propagation algorithm to rank all genes in the network by calculating the network proximity of genes to disease-related genes. Finally, an enrichment analysis was performed on drug target sets to prioritize disease-candidate drugs. It was shown that the top three drugs predicted by DTSEA, including Ataluren, Carfilzomib, and Aripiprazole, were significantly enriched in the immune response pathways indicating the potential for use as promising COVID-19 inhibitors. In addition to these drugs, DTSEA also identified several drugs (such as Remdesivir and Olumiant), which have obtained emergency use authorization (EUA) for COVID-19. These results indicated that DTSEA could effectively identify the candidate drugs for COVID-19, which will help to accelerate the development of drugs for COVID-19. We then performed several validations to ensure the reliability and validity of DTSEA, including topological analysis, robustness analysis, and prediction consistency. Collectively, DTSEA successfully predicted candidate drugs against COVID-19 with high accuracy and reliability, thus making it a formidable tool to identify potential drugs for a specific disease and facilitate further investigation.