Table 3.
Selectivity profile of compounds against human cysteine proteases.
| Cpd | 3CLpro SARS-CoV-2 IC50 μM (pIC50 ± SD)a | Human Calpain 1 IC50 μM (pIC50 ± SD)b | Cathepsin L IC50 μM (pIC50 ± SD)b |
|---|---|---|---|
| 1 | 1.46 (5.85 ± 0.05) | >300 (>3.52) | 122 (3.91 ± 0.19) |
| 1x | 1.36 (5.87 ± 0.04) | >300 (>3.52) | 42.8 (4.37 ± 0.10) |
| GC-376 | 0.02 (7.64 ± 0.27) | 0.016 (7.79 ± 0.05) | 0.0007 (9.16 ± 0.11) |
Enzymatic assays were performed with GSH (2 mM) as reducing agent. The enzymes were pre-incubated with compound at increasing concentrations before starting the reaction with the substrate. Initial rates were used to calculate % inhibitions and IC50 were obtained from concentration-response curves by a nonlinear regression analysis of the data.
a
IC50 values are averages of three independent experiments; enzyme and compound pre-incubation of 60 min.
b
IC50 values are averages of two independent experiments; enzyme and compound pre-incubation of 30 min.