Table 1. IC50 values of nirmatrelvir, ensitrelvir, and FB2001 against Mpro resistance variants.
Clear examples of single amino acid substitution mutations conferring selective resistance to nirmatrelvir and ensitrelvir are highlighted in gray; similar mutations have yet to be found for FB2001. The relative values in brackets are reflected in the heatmap in Figure 1B.
| Mpro variant |
IC50 [nM] (Fold-change relative to WT) | ||
|---|---|---|---|
| Nirmatrelvir | Ensitrelvir | FB2001 | |
| WT | 29.4 (1.0) | 35.9 (1.0) | 27.2 (1.0) |
| T21I | 36.0 (1.2) | 16.3 (0.5) | 34.0 (1.3) |
| M49I | 23.0 (0.8) | 338 (9.4) | 29.8 (1.1) |
| M49L | 27.1 (0.9) | 769 (21.4) | 10.7 (0.4) |
| L50F | 58.4 (2.0) | 21.0 (0.6) | 33.2 (1.2) |
| S144A | 236 (8.0) | 623 (17.3) | 74.7 (2.7) |
| E166A | 622 (21.2) | 126 (35.2) | 355 (13.1) |
| E166V | >10000 (>300) | 2800 (77.9) | 645 (23.7) |
| L167F | 282 (9.6) | 728 (20.3) | 115 (4.2) |
| ΔP168 | 243 (8.3) | 193 (5.4) | 184 (6.8) |
| A173V | 460 (15.8) | 45.9 (1.3) | 45.7 (1.7) |
| P252L | 76.9 (2.6) | 28.8 (0.8) | 38.9 (1.4) |
| T304I | 40.7 (1.4) | 19.0 (0.5) | 10.5 (0.4) |
| L50F/E166A | 793 (27) | 1040 (28.8) | 355 (13) |
| L50F/E166V | >10000 (>300) | 751 (20.9) | 185 (6.8) |
| ΔP168/A173V | 1630 (55.4) | 122 (3.4) | 166 (6.1) |