K777 (K11777, S-001, SLV213) is a highly potent, irreversible, covalent inhibitor of mammalian cathepsin L and other cysteine proteases of clan CA.
K777 was originally developed as an inhibitor of cathepsin S, but later showed promise as an antiparasitic agent.
K777 inhibits C. parvum growth in mammalian cell lines in a concentration-dependent manner, rescues mice from a lethal Cryptosporidium parvum infection
K777 blocked the entry of pseudovirus forms of SARS-CoV-1 and MERS into Vero E6 or HEK293 cells, likely due to inactivation of cathepsin L (CTSL) on cell surfaces and/or within endosomes.
K777 reduced SARS-CoV-2 viral infectivity in several host cells: Vero E6 (EC50< 74 nM), HeLa/ACE2 (4 nM), Caco-2 (EC90 = 4.3 μM), and A549/ACE2 (<80 nM).
