Digoxin

Digoxin is a potent inhibitor of Na+/K+-ATPase, has the potential for arrhythmia and heart failure treatment. IC50 & Target:Na+/K+ ATPase^[1] In Vitro: Digoxin, a sodium-potassium ATPase inhibitor, has a negative Z score of 26.67, suggesting a function for the sodium-potassium ATPase in CHIKV infection. Relative to DMSO-treated cells, treatment of U-2 OS cells with Digoxin results in a dose-dependent decrease in CHIKV infection with a half-maximal effective concentration (EC₅₀) of 48.8 nM. Digoxin treatment similarly decreases CHIKV infection of primary human synovial fibroblasts (HSFs) and Vero African green monkey kidney cells with EC₅₀s of 43.9 nM and 67.3 nM, respectively. Digoxin treatment significantly diminishes CHIKV infection in these cell types, with EC₅₀s of 16.2 μM in ST2 cells and 23.2 μM in C2C12 cells, values 330 and 475 times the EC₅₀ of Digoxin in U-2 OS cells. Cell viability is only modestly impaired at 24 h posttreatment with 1 μM Digoxin, a dose 20 times the Digoxin EC₅₀ for CHIKV antiviral activity in these cells^[1].