Table 1 PLpro inhibition and SARS-CoV-2 antiviral activity
From: Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2
Compound | R1a | Electrophile | IC50 (μM)b | Time dep. | kinact/KI (M−1 s−1) | EC50 (μM)c | CC50 < 30 μM |
|---|---|---|---|---|---|---|---|
GRL0617 | NH2 | NA | 1.2 | No | NA | ND | ND |
3 | H | NA | >100 | No | NA | ND | ND |
5 | H | NA | 24 | No | NA | ND | ND |
7 | H | Fumarate ester | 0.094 | Yes | 9,600 | 1.1 | No |
8 | NHAc | Fumarate ester | 0.230 | Yes | 9,000 | No CPE | No |
9 | H | Chloroacetamide | 5.4 | Yes | 110 | 34 | No |
10 | NHAc | Chloroacetamide | 4.4 | Yes | 140 | No CPE | No |
11 | H | Cyanoacetamide | 8.0 | No | ND | No CPE | No |
12 | H | Propiolamide | 0.098 | Yes | 4,100 | No CPE | Yes |
13 | H | α-cyanoacrylamide | >200 | No | ND | No CPE | Yes |
14 | H | NA | 100 | ND | NA | No CPE | No |
15 | NHAc | NA | 6.2 | ND | NA | No CPE | No |
