Invest Clin 62(4): 316 - 324, 2021 https://doi.org/10.22209/IC.v62n4a03 Corresponding author: Farnoosh Ebrahimzadeh. Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Email: ebrahimzadehf@mums.ac.ir Drug-disease interactions of differentially expressed genes in COVID-19 liver samples: an in-silico analysis Suzan Omar Rasool 1 , Ata Mirzaei Nahr 2 , Sania Eskandari 3 , Milad Hosseinzadeh 4 , Soheila Asoudeh Moghanloo 5 and Farnoosh Ebrahimzadeh 6 1 Department of Clinical Pharmacy, College of Pharmacy, University of Duhok, Kurdistan Region, Iraq. 2 School of Medical Sciences and Health Services, Tabriz University of Medical Sciences, Tabriz, Iran. 3 Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran. 4 School of Medical Sciences and Health Services, Zabol University of Medical Sciences, Zabol, Iran. 5 Department of Genetic Enginering, Marvdasht Branch, Islamic Azad University, Marvdasht. 6 Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Key words: COVID-19; liver; cytochrome P450; gene expression. Abstract. While COVID-19 liver injuries have been reported in various stud- ies, concerns are raised about disease-drug reactions in COVID-19 patients. In this study, we examined the hypothesis of gene-disease interactions in an in-silico model of gene expression to seek changes in cytochrome P450 genes. The Gene Expression Omnibus dataset of the liver autopsy in deceased COVID-19 patients (GSE150316) was used in this study. Non-alcoholic fatty liver biopsies were used as the control (GSE167523). Besides, gene expression analysis was performed us- ing the DESeq/EdgeR method. The GO databases were used, and the paths were set at p<0.05. The drug-gene interaction database (DGIdb) was searched for in- teractions. According to the results, 5,147 genes were downregulated, and 5,122 genes were upregulated in SARS-CoV-2 compared to healthy livers. Compared to the cytochromes, 34 cytochromes were downregulated, while 4 cytochromes were upregulated among the detected differentially expressed genes (DEG). The drug-gene interaction database (DGIdb) provided a list of medications with potential interactions with COVID-19 as well as metacetamol, phenethyl iso- cyanate, amodiaquine, spironolactone, amiloride, acenocoumarol, clopidogrel,