Gene Expression Network Analysis Provides Potential Targets Against SARS-CoV-2

Abstract

ABSTRACTBACKGROUNDCell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed withACE2andTMPRSS2, and to further explore their biological functions and potential as druggable targets.METHODSUsing the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions.RESULTSACE2was in a module of 681 co-expressed genes; 12 genes with moderate-high correlation withACE2(r>0.3, FDR<0.05) had known interactions with existing drug compounds.TMPRSS2was in a module of 1,086 co-expressed genes; 15 of these genes were enriched in the gene ontology biologic process ‘Entry into host cell’, and 53TMPRSS2-correlated genes had known interactions with drug compounds.CONCLUSIONDozens of genes are co-expressed withACE2andTMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may help to fast-track the development of COVID-19 therapeutics.