Table 1.
3CLpro mutations that were associated with reduced nirmatrelvir inhibitory activity of SARS-CoV-2 replication or 3CLpro activity.
| Mutation | Reduction in susceptibility of SARS-CoV-2 replication (fold change) | Reduction in inhibition of 3CLpro activity (fold change) | References |
|---|---|---|---|
| G15S | N/A | 4.4 | 14 |
| T21I | 1.1–4.6 | N/A | 11,13, 14 |
| L50F | 1.4–4.2 | N/A | 11,13, 14 |
| Y54A | N/A | 24.0 | 14 |
| Y54C | 2.6–8.3 | N/A | 16 |
| T135I | N/A | 3.2 | 14 |
| F140A | N/A | 39.0 | 14 |
| F140L | N/A | 5.4 | 14 |
| S144A | 2.2–12.2 | 20.5–92 | 11,14,18,19 |
| S144E | N/A | 470.0 | 14 |
| S144F/G/M/Y | N/A | 19.2–38.0 | 18 |
| S144T | N/A | 160.0 | 14 |
| H164N | N/A | 6.4 | 14 |
| M165T | N/A | 29.9 | 18 |
| E166A | 3.3 | 10.0–33.0 | 14,17 |
| E166G | N/A | 16.0–16.4 | 14,18 |
| E166V | 25.0–288 | N/A | 13, 14, 15 |
| L167F | 3.6–16.5 | N/A | 16,17 |
| Del P168 | 5.1 | N/A | 19 |
| H172Q/F | N/A | >42.0 | 18 |
| H172Y | 24 | >133.7 | 14,18,20 |
| A173T | 4.1 | N/A | 19 |
| A173V | 0.9–11.6 | 26.0 | 11,14,19 |
| V186G | N/A | 13.0 | 14 |
| Q189K | N/A | 65.0 | 14 |
| Q192L | 4.3 | 28.0 | 14,18 |
| Q192P | 7.6 | 33.0 | 14,18 |
| Q192T/S/A/I/H/V/W/C/F | N/A | >22.2 | 18 |
| D248E | N/A | 3.7 | 14 |
| P252L | 5.9 | N/A | 11,14 |
| T304I | 2.1–5.5 | N/A | 11,13,14 |
IC50: 50% inhibitory concentration; N/A, data not available.
This table only shows the effect of single mutations.