YH-53 is a potent 3CLpro inhibitor with Ki values of 6.3 nM, 34.7 nM for SARS-CoV-1 3CLpro and SARS-CoV-2 3CLpro, respectively. YH-53 strongly blocks the SARS-CoV-2 replication. YH-53 is a peptidomimetic compound with a unique benzothiazolyl ketone. YH-53 has the potential for COVID-19 research[2].IC50 & Target: Ki: 6.3 nM (SARS-CoV-1 3CLpro) and 34.7 nM (SARS-CoV-2 3CLpro)In Vitro: YH-53 (1-25 μM; for 24 h) efficiently reduces copies of total RNA with increased concentrations in VeroE6/TMPRSS2 cells.
YH-53 (1, 5, 10, 15, 20, 25 μM; for 48 h) with 10 μM completely blocks the viral proliferation against SARS-CoV-2 were examined by a cytopathic effect (CPE) assay in Vero cells.
YH-53 (10, 100 μM; for 24 h) has no cytotoxicity with a CC50 value of >100 μM in vero cells.
YH-53 (10 μM) moderately inhibits CYP1A2, CYP2D6, and CYP2C8 (26.6%, 38.0%, 66.4%, respectively). YH-53 has no inhibition on CYP2C9 and CYP3A4.
YH-53 inhibits SARS-CoV 3CLpro with an IC50 of 0.74 μM.In Vivo: YH-53 (0.1 mg/kg; iv) has a T1/2 of 2.97 hours, an AUC0–∞ of 19.7 ng?h/mL, a Vd of 3.51 L/kg in rats.
YH-53 (0.5 mg/kg; oral) has a T1/2 of 9.64 hours, an AUC0–∞ of 3.49 ng?h/mL, a Cmax of 1.08 ng/mL in rats.