The COVID-19 crisis called for rapid reaction from all the fields of biomedical research. Traditional drug development involves time consuming pipelines that conflict with the urgence of identifying effective therapies during a health and economic emergency. Drug repositioning, that is the discovery of new clinical applications for drugs already approved for different therapeutic contexts, could provide an effective shortcut to bring COVID-19 treatments to the bedside in a timely manner. Moreover, computational approaches can help accelerate the process even further. Here we present the application of computational drug repositioning tools based on transcriptomics data to identify drugs that are potentially able to counteract SARS-CoV-2 infection, and also to provide insights on their mode of action. We believe that mucolytics and HDAC inhibitors warrant further investigation. In addition, we found that the DNA Mismatch repair pathway is strongly modulated by drugs with experimental in vitro activity against SARS-CoV-2 infection. Both full results and methods are publicly available.