Integrated transcriptomic analyses identifies host-targeting repurposing drugs for hepatitis C virus infection and related hepatocellular carcinoma

Hepatitis C virus (HCV) infection is a major risk factor in developing hepatocellular carcinoma (HCC). Drug development for HCV infection and HCC treatment is needed owing to treatment failure due to viral resistance and tumor heterogeneity. We analysed transcriptomic data of human liver tissues from multiple studies to identify differentially expressed genes in four study groups: (HCV+ vs Control); (HCV+HCC+ vs Control); (HCV+ AND HCV+HCC+ vs Control); and (HCV+HCC+ vs HCV+) respectively. We identified 597, 1321, 923, and 1526 upregulated and 474, 558, 336, and 989 downregulated genes for above respective studied groups. We performed functional, pathway enrichment, and protein-protein interaction analyses for identified upregulated genes. We identified and prioritized 39, 57, 58, and 110 repurposing drugs for 9, 17, 14, and 33 non-essential upregulated target genes based on drug group, action, and literature evidence. We also performed mutational analysis of key target genes. We found several dysregulated genes such as CTLA4 , GPC3 , MDK , TUBB2B etc. and many novel target genes like CACNB4 , HTR7 , IGHG1 , SLC22A12, etc. We identified several potential repurposing drugs namely asenapine, cabergoline, dequalinium, epinastine, methysergide, loxapine, lurasidone, etc. This study identified prospective repurposing drugs using host-targeting approach for HCV infection and related HCC treatment.