Table 2. Resistance phenotypes of Mpro variants using the VSV-based cis-cleavage system.
Fold resistance is calculated by relative IC50 versus WT in assays ran in parallel.
| 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 (10.8–11.7) | – | 12.9 (12.2–14.4) | – |
| T45I | 13.0 (112–15.4) | <2 | 48.1 (45.9–50.7) | 3.7 |
| D48Y | 15.7 (14.6–17.1) | <2 | 27.5 (26.0–28.7) | 2.1 |
| M49I | 4.1 (3.8–4.4) | <2 | >100* | >10* |
| M49L | 6.7 (6.5–6.9) | <2 | >100* | >10* |
| ∆P168 | 35.5 (32.2–47.2) | 7.1 | 19.1 (16.9–20.1) | 3.5 |
| A173T | 45.3 (40.0–55.2) | 4.0 | 18.8 (18.3–19.3) | <2 |
| A173V | 82.6 (59.5–93.5) | 7.4 | 10.3 (3.8–27.3) | <2 |
| ∆P168/A173V | >100* | >10* | 37.4 (33.2–43.0) | 3.1 |
| T45I/∆P168 | >100* | >10* | >100* | >10* |
| T45I/A173V | >100* | >10* | 27.4 (24.2–29.6) | 2.2 |
| D48Y/∆P168 | >100* | >10* | >100* | >10* |
| M49I/∆P168 | 33.1 (32.0–34.2) | 3.0 | >100* | >10* |
*Estimated value due to highest drug concentration failing to restore 50% activity.