Off-target profiling using computational approaches has been widely used to identify candidates for drug repurposing. Indeed, JAK inhibitors were recently established as potential candidate therapies for SARS-CoV-2 based on in silico methods.(52-54) Our computational methods identified 98 drug-target predictions, and the preliminary in vitro results found inhibitory activity on several proteins other than the primary therapeutic target, thereby confirming baricitinib and tofacitinib as promiscuous drugs and candidates for drug repurposing studies. For example, PDE10A inhibition has been primarily studied in psychiatric and neurological conditions, such as schizophrenia and Huntington's disease, and, to a lesser extent, in multiple peripheral pathological conditions(59,60) (e.g., osteogenic differentiation). Additionally, PDE10A inhibition by baricitinib is hypothesized to have a synergistic pharmacological effect in combination with other COVID-19 treatments (e.g., antiviral and corticosteroids drugs), due to the antifibrotic and anti-inflammatory effects of phosphodiesterase's inhibitors on the treatment of COVID-19 and its associated conditions (e.g., thrombosis, inflammation, and fibrosis).(61,62) Therefore, the confirmed PDE10A inhibition identified in this study supports the potential for baricitinib as a potential candidates outside of rheumatology.