Abstract Background Severe acute respiratory syndrome coronavirus (SARS-CoV-2), an emerging Betacoronavirus, is the causative agent of COVID-19. Angiotensin converting enzyme 2 (ACE2), being the main cell receptor of SARS-CoV-2, plays a role in the entry of the virus into the cell. Currently, there are neither specific antiviral drugs for the treatment or preventive drugs such as vaccines. Methods We proposed a bioinformatics analysis to test in silico existing drugs as a fast way to identify an efficient therapy. We performed a differential expression analysis in order to identify differentially expressed genes in COVID-19 patients correlated with ACE-2 and we explored their direct relations with a network approach integrating also drug-gene interactions. The drugs with a central role in the network were also investigated with a molecular docking analysis. Results We found 825 differentially expressed genes correlated with ACE2. The protein-protein interactions among differentially expressed genes identified a network of 474 genes and 1130 interactions. Conclusions The integration of drug-gene interactions in the network and molecular docking analysis allows us to obtain several drugs with antiviral activity that, alone or in combination with other treatment options, could be considered as therapeutic approaches against COVID-19.