Computational Drug Repositioning and Elucidation of Mechanism of Action of Compounds against SARS-CoV-2
byFrancesco Napolitano, Gennaro Gambardella, Xin Gao, Diego di Bernardo
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.