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 demonstrates potent activity in reducing total RNA copies in VeroE6/TMPRSS2 cells, with efficiency increasing at concentrations between 1-25 μM over 24 hours [1]. Notably, YH-53 effectively inhibits viral proliferation of SARS-CoV-2 in Vero cells, particularly at a concentration of 10 μM over 48 hours, as evidenced by a cytopathic effect (CPE) assay, without exhibiting cytotoxicity at concentrations up to 100 μM [1]. Additionally, YH-53 moderately suppresses the activity of CYP1A2, CYP2D6, and CYP2C8 by 26.6%, 38.0%, and 66.4%, respectively, while not affecting CYP2C9 and CYP3A4 [1]. Moreover, it inhibits SARS-CoV 3CL pro with an IC50 of 0.74 μM [1]. This evidence underscores YH-53's potential as a selective and effective inhibitor for research in viral replication and metabolic enzyme interaction contexts.

YH-53, administered to rats, demonstrates varied pharmacokinetic properties based on the route of administration. Intravenously at 0.1 mg/kg, YH-53 shows a half-life (T 1/2) of 2.97 hours, an area under the curve (AUC 0–∞) of 19.7 ng·h/mL, and a distribution volume (V d) of 3.51 L/kg. When given orally at 0.5 mg/kg, it exhibits a T 1/2 of 9.64 hours, an AUC 0–∞ of 3.49 ng·h/mL, and a maximum concentration (C max) of 1.08 ng/mL in rats. These findings provide useful insights into the compound's pharmacokinetics, indicating significant differences in half-life, distribution, and absorption rates between intravenous and oral administration in this animal model [1].