Table 1 Comparison of DV-19-2a with current benchmark SARS-CoV-2 3CL protease non-covalent inhibitors
Compound | SARS-CoV-2 3CLpro IC50 (µM) | SARS-CoV-2 antiviral EC50 (µM) | Off-target effects on human proteases | Pan- Coronavirus Activity | Resolution of co-crystal structure with SARS-CoV-2 3CLpro (Å) | Reference |
|---|---|---|---|---|---|---|
Analog 29 | 0.04 | 0.3 | IC50 > 10 µM on a panel of human proteases | SARS-CoV MERS-CoV | 1.52 | |
S‐217622 (Ensitrelvir) | 0.01 | 0.1 | IC50 > 100 µM on a panel of human proteases | SARS-CoV MERS-CoV HCoV-OC43 HCoV-229E | 1.80 (7VU6) | Journal of Medicinal Chemistry 20229 |
WU-04 | 0.02 | 0.03 | Not determined | SARS-CoV MERS-CoV | 1.83 (7EN8) | ACS central science 202322 |
CCF981 | 0.05 | 0.3 | Not determined | Not determined | Not determined | Journal of Medicinal Chemistry 202223 |
GC-14 | 0.05 | 1.0 | IC50 > 50 µM on a panel of human proteases | SARS-CoV | 1.40 (8ACL) | Journal of Medicinal Chemistry 202224 |
JZD-07 | 0.15 | 0.82 | IC50 > 100 µM on a panel of human proteases | Not determined | 1.80 (8GTV) | Signal Transduction and Targeted Therapy 202325 |
Compound 11a | 102 | Not determined | Not determined | Not determined | Not determined | Pharmaceuticals 202226 |
Compound 23 R (Jun8-76-3A) | 0.2 | 1.3 | IC50 = 6 µM (calpain 1) IC50 = 11 µM (cathepsin L) | SARS-CoV | 2.60 (7KX5) | Journal of American Chemical Society 202127 |
ML188 | 2.5 | 13 | Not determined | SARS-CoV | 2.39 (7L0D) | Viruses 202128 |
Compound 7 | 5.7 | 40 | Not determined | Not determined | Not determined | Bioorganic & Medicinal Chemistry Letters 202129 |
