Table 2.
Inhibition of nirmatrelvir and ensitrelvir against SARS-CoV-2 Mpro polymorphisms
| Polymorphism | Nirmatrelvir |
Ensitrelvir |
||||
|---|---|---|---|---|---|---|
| IC50 (nM) | Ki (nM) | Ki fold increase | IC50 (nM) | Ki (nM) | Ki fold increase | |
| M49I | 17.1 ± 0.5 | 10.4 ± 0.87 | 1.60 | 139 ± 8 | 54.2 ± 7.8 | 6.09 |
| M49T | 16.9 ± 0.5 | 9.6 ± 1.15 | 1.48 | 73.0 ± 0.3 | 31.6 ± 3.8 | 3.55 |
| N142S | 29 ± 1 | 11.5 ± 1.57 | 1.77 | 67 ± 2 | 40.4 ± 3.3 | 4.54 |
| N142D | 32 ± 1 | 16.45 ± 1.90 | 2.53 | 48.0 ± 0.2 | 23.2 ± 1.9 | 2.61 |
| G143S | 3380 ± 128 | 960.2 ± 237 | 147.7 | 197 ± 0.5 | 141.3 ± 17 | 15.9 |
| M165I | 19 ± 1 | 11.1 ± 0.99 | 1.71 | 32.0 ± 0.4 | 13.9 ± 0.9 | 1.56 |
| R188K | 17 ± 1 | 9.0 ± 1.22 | 1.38 | 38 ± 3 | 17.2 ± 2.1 | 1.93 |
| R188S | 61 ± 3 | 18.95 ± 3.11 | 2.92 | 74 ± 1 | 51.3 ± 3.5 | 5.76 |
| Q189K | 203 ± 16 | 106.7 ± 14.9 | 16.4 | 38 ± 9 | 8.3 ± 2.4 | 0.93 |
| T190I | 25 ± 1 | 13.2 ± 1.38 | 2.03 | 44 ± 2 | 21.6 ± 2.7 | 2.43 |
| A191T | 27 ± 1 | 13.2 ± 1.43 | 2.03 | 67 ± 2 | 34.6 ± 3.2 | 3.89 |
| A191V | 46 ± 2 | 16.9 ± 2.45 | 2.60 | 48.0 ± 0.1 | 30.7 ± 2.1 | 3.45 |
| A193S | 27 ± 1 | 15.8 ± 2.15 | 2.43 | N.D. | N.D. | N.D. |
| A193T | 32 ± 1 | 18.2 ± 2.75 | 2.80 | N.D. | N.D. | N.D. |
| A193V | 11 ± 2 | 4.8 ± 1.3 | 0.74 | N.D. | N.D. | N.D. |
| Wildtype | 21.9 ± 0.4 | 6.5 ± 0.46 | 1 | 13 ± 1 | 8.9 ± 0.71 | 1 |
IC50 fold increase is relative to the WT. Data in table are means ± SD.
Abbreviation: N.D., not determined.