YH-53 is a potent 3CLpro inhibitor, exhibiting K i values of 6.3 nM and 34.7 nM against SARS-CoV-1 3CLpro and SARS-CoV-2 3CLpro, respectively. This peptidomimetic compound, characterized by its unique benzothiazolyl ketone structure, significantly inhibits SARS-CoV-2 replication, highlighting its potential in COVID-19 research [1] [2].

YH-53 (1-25 μM; for 24 h) potently reduces copies of total RNA with increased concentrations in VeroE6/TMPRSS2 cells [1]. 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 [1]. YH-53 (10, 100 μM; for 24 h) has no cytotoxicity with a CC 50 value of >100 μM in vero cells [1]. 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 [1]. YH-53 inhibits SARS-CoV 3CL pro with an IC 50 of 0.74 μM. RT-PCR [1] Cell Line: VeroE6/TMPRSS2 cells Concentration: 1, 5, 10, 15, 20, 25 μM Incubation Time: 24 hours Result: Efficiently reduced copies of total RNA.

YH-53 (0.1 mg/kg; iv) exhibits a T 1/2 of 2.97 hours, an AUC 0–∞ of 19.7 ng h/mL, a V d of 3.51 L/kg in rats [1]. YH-53 (0.5 mg/kg; oral) exhibits a T 1/2 of 9.64 hours, an AUC 0–∞ of 3.49 ng h/mL, a C max of 1.08 ng/mL in rats [1]. Animal Model: Rats [1] Dosage: 0.1 mg/kg (Pharmacokinetic Analysis) Administration: IV Result: Had a T 1/2 of 2.97 hours, an AUC 0–∞ of 19.7 ng h/mL, a V d of 3.51 L/kg.