Notably, antiviral assays show that the combination of two compounds, nafamostat, and K777, which simultaneously blocked TMPRSS2- and CTSL/CTSB-mediated viral entry pathways exhibited synergistic antiviral activity against SARS-CoV-2, indicating that dual-inhibition is an effective strategy for clinical development to treat COVID-19. This evidence concerns the gene CTSL and COVID-19.