Discovery of potential drugs for COVID-19 based on the connectivity map

Abstract Background: Corona virus infective disease 19 (COVID-19) is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spreads very rapidly, which become a worldwide public healthy crisis. Until now, there is no effective antivirus drugs or vaccines specifically used for its treatment. So it is urgent to discover efficient therapeutic methods. The same as SARS-CoV, SARS-CoV-2 also invades organism by combining with Angiotensin-converting enzyme 2 (ACE2). Recently, there are reports about SARS-CoV-2 infected host not only through the respiratory tract, but also gastrointestinal tract. However, it is proved that ACE2 plays a key role in protecting subjects from lung injury and resisting the inflammation caused by intestinal epithelial damage. Interestingly, the expression of ACE2 protein is reduced after SARS-CoV infection. Methods: According to the dataset of genes co-expressed with ACE2 in the colonic epithelial cells, we established a protein-protein interaction (PPI) Network and selected hub genes from them. The cluster analysis was performed to find out the dense region of the PPI Network. Then, gene ontology (GO) and pathway enrichment analysis were performed to explore the main function of genes co-expressed with ACE2. Finally, we predicted the potential drugs for the treatment of COVID-19 based on the connectivity map (Cmap) . Results: We constructed a PPI network containing 125 hub genes of genes co-expressed with ACE2 in the colonic epithelial cells and obtained two modules through cluster analysis. The GO analysis and the KEGG pathway revealed these genes were aggregated in ribosome, exosomes, extracellular cellular components; structure constituent of ribosome, G-protein coupled receptor activity, MHC class I and II receptor activity biological processes; immune response, protein metabolism, signal transduction biological processes; and ribosome, graft-versus-host disease, viral myocarditis pathways. The result from Cmap indicated ikarugamycin, molsidomine had highly correlated scores with the query files. Conclusion: We found out that ikarugamycin and molsidomine were the potential drugs for the treatment of COVID-19.