Drug interactions with other drugs are a well-known phenomenon. Similarly, however, pre-existing drug therapy can alter the course of diseases for which it has not been prescribed. We performed network analysis on drugs and their respective targets to investigate whether there are drugs or targets with protective effects in COVID-19, making them candidates for repurposing. These networks of drug-disease interactions (DDSIs) and target-disease interactions (TDSIs) revealed a greater share of patients with diabetes and cardiac co-morbidities in the non-severe cohort treated with dipeptidyl peptidase-4 (DPP4) inhibitors. A possible protective effect of DPP4 inhibitors is also plausible on pathophysiological grounds, and our results support repositioning efforts of DPP4 inhibitors against SARS-CoV-2. At target level, we observed that the target location might have an influence on disease progression. This could potentially be attributed to disruption of functional membrane micro-domains (lipid rafts), which in turn could decrease viral entry and thus disease severity.
Keywords: COVID-19; DPP4 inhibitors; drug repurposing; drug-disease interaction; lipid rafts; network analysis; target-disease interaction.