YH-53 is a potent peptidomimetic 3CLpro inhibitor featuring a unique benzothiazolyl ketone pharmacophore that displays low-nanomolar inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases and effectively blocks SARS-CoV-2 replication, thereby providing a structurally distinctive and mechanistically validated compound for antiviral and COVID-19 research.

In enzymatic assays, YH-53 inhibited SARS-CoV-1 and SARS-CoV-2 3CLpro with Ki values of 6.3 nM and 34.7 nM respectively. In VeroE6/TMPRSS2 cells, it dose-dependently reduced viral RNA copies and inhibited proliferation (10 μM), showing moderate inhibition of CYP2C8/2D6/1A2 but no effect on CYP2C9/3A4 [1].

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].

DMSO: 40 mg/mL (69.48 mM), Sonication is recommended.