The proteases TMPRSS2 (transmembrane protease serine 2) and furin are known to play important roles in viral infectivity including systematic COVID-19 infection through priming of the spike protein of SARS-CoV-2 and related viruses. To discover small-molecules capable of inhibiting these host proteases, we established convenient and cost-effective cell-based assays employing Vero cells overexpressing TMPRSS2 and furin. A cell-based proteolytic assay for broad-spectrum protease inhibitors was also established using human prostate cancer cell line LNCaP. Evaluation of camostat, nafamostat, and gabexate in these cell-based assays confirmed their known TMPRSS2 inhibitory activities. Diminazene, a veterinary medicinal agent and a known furin inhibitor was found to inhibit both TMPRSS2 and furin with IC50s of 1.35 and 13.2 μM, respectively. Establishment and the use of cell-based assays for evaluation TMPRSS2 and furin inhibitory activity and implications of dual activity of diminazene vs TMPRSS2 and furin are presented.