TABLE 1.
Inhibitory activity of oseltamivir and zanamivir on mixed populations of NAI-susceptible and -resistant recombinant influenza B viruses with single-nucleotide substitutions in NA
| NAI | Resistant virus (%)a | Mean IC50 (nM) ± SD for influenza B viruses with single NA substitutionsb |
|||||
|---|---|---|---|---|---|---|---|
| E119A | D198E | I222T | H274Y | N294S | R371K | ||
| Oseltamivir | 0 | 5.9 (1) | 5.9 (1) | 5.9 (1) | 5.9 (1) | 5.9 (1) | 5.9 (1) |
| 10 | 8.3 ± 1.7 (1) | 43.2 ± 0.1 (7) | 22.6 ± 5.0 (4) | 14.2 ± 1.2 (2) | 29.5 ± 5.6 (5) | 9.1 ± 0.7 (2) | |
| 20 | 6.9 ± 0.6 (1) | 60.2 ± 0.2 (10) | 29.3 ± 2.1 (5) | 16.0 ± 0.5 (3) | 62.0 ± 8.7 (11) | 9.3 ± 0.7 (2) | |
| 50 | 8.1 ± 0.7 (1) | 69.5 ± 0.3 (12) | 54.8 ± 6.4 (9) | 32.9 ± 1.4 (6) | 112.9 ± 11.3 (19) | 35.3 ± 2.2 (6) | |
| 80 | 51.7 ± 8.4 (9) | 57.0 ± 5.9 (10) | 77.5 ± 7.1 (13) | 46.8 ± 0.2 (8) | 149.9 ± 1.5 (25) | 199.6 ± 32.8 (34) | |
| 100 | 12,532.5 ± 750.6 (2124) | 54.4 ± 0.5 (9) | 75.2 ± 7.2 (13) | 43.5 ± 5.6 (7) | 167.2 ± 13.1 (28) | 385.7 ± 4.9 (65) | |
| Zanamivir | 0 | 1.1 (1) | 1.1 (1) | 1.1 (1) | 1.1 (1) | 1.1 (1) | 1.1 (1) |
| 10 | 1.0 ± 0.1 (1) | 1.3 ± 0.1 (1) | 1.2 ± 0.0 (1) | 0.9 ± 0.0 (1) | 0.7 ± 0.6 (1) | 1.0 ± 0.2 (1) | |
| 20 | 1.0 ± 0.0 (1) | 1.7 ± 0.3 (2) | 1.4 ± 0.1 (1) | 0.8 ± 0.0 (1) | 2.2 ± 0.1 (2) | 1.3 ± 0.2 (1) | |
| 50 | 1.3 ± 0.2 (1) | 2.0 ± 0.2 (2) | 1.7 ± 0.1 (2) | 0.7 ± 0.1 (1) | 3.0 ± 0.3 (3) | 4.3 ± 0.4 (4) | |
| 80 | 3.5 ± 0.1 (3) | 2.6 ± 0.3 (2) | 2.0 ± 0.2 (2) | 0.6 ± 0.1 (1) | 3.5 ± 0.2 (3) | 37.3 ± 0.0 (34) | |
| 100 | 6,260.0 ± 1,026.6 (5,690) | 2.6 ± 0.5 (2) | 1.4 ± 0.1 (1) | 0.5 ± 0.1 (1) | 3.9 ± 0.9 (4) | 65.7 ± 7.0 (60) | |
a
NAI-susceptible (rg-WT) and -resistant influenza B viruses were mixed in different ratios (on the basis of PFU).
b
Data were collected in fluorescence-based assays; the values shown were calculated from two independent experiments. Substitutions are identified by N2 numbering. Data in parentheses represent the fold increase over the value for the WT.