LY1 is a potent, selective and covalent inhibitor against both SARS-CoV-2 PLpro and Mpro with Kd values of 1.5 μM and 2.3 μM for Mpro C145A protein and PLpro C111A protein, respectively. LY1 potent against the viral proteases, with IC50s of 0.12 μM and 0.99 μM against Mpro and PLpro. LY1 shows high selectivity over other kinases, human proteases and metalloenzyme.
In SARS-CoV-2-infected Vero E6 cells, LY1 causes a dramatic reduction in the viral nucleoprotein (NP) levels with 5 μM. A 99.99% reduction in the viral RdRP RNA levels is observed with 15 μM LY1[1].
LY1 against cathepsin B and cathepsin L with the IC50 values of 8.8 μM and 2.2 μM, respectively[1].
In the 8 week toxicity study, rats are orally administered with LY1 up to 300 mg/kg for 4 weeks and then recovered for another 4 weeks; no significant change in body weight and food consumption is observed in any group[1].
References:
[1]. Wenying Yu, et al. Structure-Based Design of a Dual-Targeted Covalent Inhibitor Against Papain-like and Main Proteases of SARS-CoV-2. J Med Chem. 2022 Dec 22;65(24):16252-16267.