Table 1.
SARS-CoV-2 3CLpro inhibition of hit compound 1 and analogs 1A-D, 1x.
| Cpd | Assay without GSH |
Assay with GSH |
||
|---|---|---|---|---|
| IC50 (μM) | pIC50 ± SD | IC50 (μM) | pIC50 ± SD | |
| 1 | 0.021 | 7.67 ± 0.30 | 1.46 | 5.85 ± 0.05 |
| 1A | 35.000 | 4.46 ± 0.19 | >100 | <4 |
| 1B | 0.178 | 6.75 ± 0.63 | 22.40 | 4.65 ± 0.07 |
| 1C | 0.023 | 7.65 ± 0.32 | 9.36 | 5.03 ± 0.10 |
| 1D | >100 | <4 | >100 | <4 |
| 1x | 0.027 | 7.57 ± 0.22 | 1.36 | 5.87 ± 0.04 |
Enzymatic assays were performed with or without GSH 2 mM in the buffer. The enzyme was pre-incubated for 1 hour with compound at increasing concentrations before starting the reaction with the substrate. Initial rates were recorded to calculate % inhibition and IC50 were obtained from concentration-response curves by a nonlinear regression analysis of the data. IC50 values are averages of three independent experiments.