Two main proteases for both SARS-S and SARS-2-S are endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane protease, serine 2TMPRSS2 [16]. In 293 T cells lacking 2TMPRSS2, blocking CatB/L activity through increasing the endosomal pH by ammonium chloride could significantly limit the entry of both SARS-S and SARS-2-S. In TMPRSS2 + Caco-2 cells, the effect of ammonium chloride existed to a lesser extent. A combination of camostat mesylate, a blocker of TMPRSS2, and E-64d, an inhibitor of CatB/L, yielded the complete inhibition of SARS-2-S entry in TMPRSS2 + Caco-2 cells. In both the human lung cancer cell line Calu-3 and the primary human lung cells, there was a reduction of the entry of both SARS-S and SARS-2-S by camostat mesylate, indicating that SARS-S and SARS-2-S partially require TMPRSS2 for a lung infection.