Coranastat (NK01-63) is a GC376 analog with improved potency, and highly potent, selective SARS-CoV-2 3CL protease inhibitor with IC50 of 16 nM, exhibits antiviral potency with EC50 of 6 nM in Huh-7ACE2 cellular assays.
NK01-63 exhibited outstanding improvements over GC376 for inhibiting SARS-CoV-2 in vitro and in cells, demonstrated high potency in human Caco-2 cells against SARS-CoV-2 infection with EC90 of 81 nM.
NK01-63 is highly selective for 3CL inhibition, displaying IC50 values of >100 μM against many of the other human proteases and possessing only modest levels of inhibition of caspase 8 (IC50=18 µM), cathepsin B (IC50=1.1 µM), cathepsin K (IC50=0.04 µM), and cathepsin S (IC50=0.03 uM), but with high potency against cathepsin L (IC50=0.006 uM).
NK01-63 exhibits specific pan-coronavirus activities, can effectively block the viral replication of human coronavirus alpha OC43 and human coronavirus beta 229E, with EC50 values < 100 nM in Huh-7 human cells, also blocks replication of MERS-CoV (EC50< 1 µM) and SARS-CoV (EC50< 3 µM) in Vero 76 cells.