Cell 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 with ACE2 and TMPRSS2 , and to further explore their biological functions and potential as druggable targets. Using 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. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR < 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process ‘receptor-mediated endocytosis’, and 52 TMPRSS2- correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2 , many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.
【저자키워드】 Risk factors, Pathogenesis, genetics, TMPRSS2, 【초록키워드】 COVID-19, ACE2, bioinformatics, drugs, angiotensin-converting enzyme 2, COVID-19 therapeutics, Novel coronavirus, biological function, pathophysiology, Biology, Ontology, network analysis, targets, transmembrane serine protease 2, correlation, interactions, WGCNA, biologic, compounds, Interaction, angiotensin, Gene expression profiles, host cell, Serine, enzyme, cell entry, transmembrane serine protease, module, gene expression profile, lung tissue samples, Genes, identify, performed, facilitated, correlated, accelerate, co-expressed, entry of SARS-CoV-2, 【제목키워드】 SARS-CoV-2, network analysis, target, expression, provide,