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

By Ana I Hernandez Cordero, Xuan Li, Chen Xi Yang, Stephen Milne, Yohan Bossé, Philippe Joubert, Wim Timens, Maarten van den Berge, David Nickle, Ke Hao, Don D. Sin

Posted 06 Jul 2020
bioRxiv DOI: 10.1101/2020.07.06.182634

BACKGROUND: 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. METHODS: 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. RESULTS: ACE2 was in a module of 681 co-expressed genes; 12 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; 15 of these genes were enriched in the gene ontology biologic process Entry into host cell, and 53 TMPRSS2-correlated genes had known interactions with drug compounds. CONCLUSION: 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 help to fast-track the development of COVID-19 therapeutics. ### Competing Interest Statement S.M. reports personal fees from Novartis and Boehringer-Ingelheim, outside the submitted work. W.T. reports fees to Institution from Roche-Ventana, AbbVie, Merck-Sharp-Dohme and Bristol-Myers-Squibb, outside the submitted work. M.B. reports research grants paid to University from Astra Zeneca, Novartis, outside the submitted work. D.D.S. reports research funding from AstraZeneca and received honoraria for speaking engagements from Boehringer Ingelheim and AstraZeneca over the past 36 months, outside of the submitted work.

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