Title : Identification of potential drug targets to treat COVID-19 patients
Abstract:
Background: The emergence of Covid-19 is a cause of death for millions of people worldwide due to the cytokine storm. Therefore, we decided to work on potential drug targets for Covid-19 by understanding the biological nature of genes that are related to the infection of SARS patients.
Objective: This study aimed at understanding gene expression, pathway, and network in order to find potential drug targets for the treatment of Covid19.
Methods: We identified genes which are differentially expressed in three gene sets, GSE30589, GSE33267, and GSE47963 using GEO2R with log2FC <-1.5 for down regulated genes and log2FC >1.5 for up regulated genes. Next, we found common differentially expressed genes for pathway analysis using the “Gene Set enrichment Analysis” tool in Webgestalt and did network construction using String and Cytoscape. Then we identified the crucial genes in the pathways and hub genes in the network for drug targets. After that, we prepared and did molecular docking using Pymol and PyRx to identify the drugs with good binding affinity.
Results: We found 41common differentially expressed genes. Among them, 8 genes cytokine-cytokine interaction pathways and 9 hub genes. We also found 33 drugs as potential targets. After docking, there were two drugs with good binding affinity: Deleobuvir binds to IFNL3 (Kd=2.75208 x 10-7) and Dasabuvir binds to IFNL3 (Kd=4.48006 x 10-7). Additionally, the two drugs: Gemfibrozil and Ibudilast, which interact with IL-6 (Kd= 1.82521 x 10-4 and Kd= 1.31895 x 10-4) can suppress the secretion of the inflammatory cytokines so they also have potential for reducing the severe inflammation symptoms of Covid19.
Conclusions: Deleobuvir, Dasabuvir, Gemfibrozil, and Ibudilast can be potential drug targets for the treatment of Covid19.
