Aloxistatin [E-64d] is a cell permeable irreversible inhibitor of lysosomal and cytosolic cysteine proteases cathepsin B an L, calpain 1/2, papain and has diverse biological activities. It is an ethyl ester form of E-64c that inhibits calpain and the cysteine proteases cathepsins F, K, B, H, and L. Aloxistatin has anticancer properties by inducing cell cycle arret at the G2/M phase in A431 human epidermoid carcinoma cells and as a lysosomal inhibitor in human acute promyelocytic leukemia NB4 cells and Huh-7 cells. It inhibits degradation of autophagic cargo inside autolysosomes. It also shows neuroprotective and anti-malarial properties. Since cysteine protease cathepsin L is required for SARS-CoV-2 viral entry, aloxistatin treatment reduces cellular entry of SARS-CoV-2 pseudovirions and COVID-19. It inhibits severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 surface glycoprotein incorporation into pseudotyped vesicular stomatitis virus (VSV) particles in Vero cells. Is has been applied in vitro in combination with the TMPRSS2 inhibitor camostat mesylate (Prod. No. AG-CR1-3716).