Table 2:
Resistance phenotypes of Mpro variants using the VSV-based cis-cleavage system.
| Mpro variant | Nirmatrelvir | Ensitrelvir | ||
|---|---|---|---|---|
| IC50 μM (95% CI) | Fold-resistance (relative to WT) | IC50 μM (95% CI) | Fold-resistance (relative to WT) | |
| WT | 11.2 (10.8 to 11.7) | - | 12.9 (12.2 to 14.4) | - |
| T45I | 13.0 (112 to 15.4) | <2 | 48.1 (45.9 to 50.7 | 3.7 |
| D48Y | 15.7 (14.6 to 17.1) | <2 | 27.5 (26.0 to 28.7) | 2.1 |
| M49I | 4.1 (3.8 to 4.4) | <2 | >100* | >10* |
| M49L | 6.7 (6.5 to 6.9) | <2 | >100* | >10* |
| ΔP168 | 35.5 (32.2 to 47.2) | 7.1 | 19.1 (16.9 to 20.1) | 3.5 |
| A173T | 45.3 (40.0 to 55.2) | 4.0 | 18.8 (18.3 to 19.3) | <2 |
| A173V | 82.6 (59.5 to 93.5) | 7.4 | 10.3 (3.8 to 27.3) | <2 |
| ΔP168/A173V | >100* | >10* | 37.4 (33.2 to 43.0) | 3.1 |
| T45I/ΔP168 | >100* | >10* | >100* | >10* |
| T45I/A173V | >100* | >10* | 27.4 (24.2 to 29.6) | 2.2 |
| D48Y/ΔP168 | >100* | >10* | >100* | >10* |
| M49I/ΔP168 | 33.1 (32.0 to 34.2) | 3.0 | >100* | >10* |
Fold-resistance is calculated by relative IC50 versus WT in assays ran in parallel (*, asterisk indicates an estimated value due to highest drug concentration failing to restore 50% activity).