Table 3.
Extraction of NA amino acid mutations associated with reduced susceptibility by NAIs
| Virus | Season | Sample | AA mutation | Catalytic site | IC50 (nmol/L) | ||||
|---|---|---|---|---|---|---|---|---|---|
| Oseltamivir | Peramivir | Zanamivir | Laninamivir | Reference | |||||
| Culture‐induced mutation | |||||||||
| A/H3N2 | 2011‐2012 | DS2‐35 | T148I | 0.5 | 0.6 | 1.4 | 2.0 | 23 | |
| DS2‐44 | T148I | 0.5 | 0.6 | 1.3 | 1.9 | ||||
| DS2‐113 | T148I | 0.9 | 1.0 | 2.2 | 3.8 | ||||
| DS2‐209 | T148I | 0.5 | 0.6 | 1.7 | 1.8 | ||||
| DS2‐393 | T148I | 0.8 | 0.8 | 2.1 | 3.4 | ||||
| DS2‐516 | T148I | 0.5 | 0.8 | 2.3 | 1.8 | ||||
| DS2‐94 | T148I | 0.3 | 0.3 | 1.0 | 1.2 | ||||
| DS2‐415 | D151G | Catalytic site | 0.8 | 0.8 | 1.9 | 2.9 | 22 | ||
| DS2‐94 | D151N | Catalytic site | 0.3 | 0.3 | 1.0 | 1.2 | 22 | ||
| 2012‐2013 | DS3‐34 | T148I | 0.4 | 0.8 | 1.0 | 2.9 | |||
| DS3‐229 | T148I | 0.8 | 0.6 | 1.7 | 2.8 | ||||
| DS3‐94 | T148I | 0.9 | 1.0 | 2.3 | 4.0 | ||||
| DS3‐4 | D151N | Catalytic site | 1.0 | 0.8 | 2.4 | 3.0 | |||
| DS3‐51 | D151N | Catalytic site | 0.6 | 0.7 | 1.1 | 3.9 | |||
| DS3‐122 | D151N | Catalytic site | 0.8 | 0.8 | 2.3 | 4.4 | |||
| DS3‐360 | D151N | Catalytic site | 0.9 | 0.7 | 2.1 | 3.3 | |||
| 2013‐2014 | DS4‐9 | T148I | 0.7 | 0.6 | 1.9 | 2.2 | |||
| DS4‐354 | D151N | Catalytic site | 0.8 | 0.8 | 2.4 | 2.4 | |||
| 2014‐2015 | None | ||||||||
| 2015‐2016 | DS6‐47 | D151G | Catalytic site | 1.0 | 0.8 | 2.1 | 4.5 | ||
| 2016‐2017 | DS7‐298 | D151G | Catalytic site | 0.9 | 0.6 | 1.9 | 4.8 | ||
| DS7‐6 | D151G | Catalytic site | 0.5 | 0.4 | 1.6 | 1.6 | |||
| Drug resistance‐related mutation | |||||||||
| A/H1N1pdm09 | 2013‐2014 | DS4‐549 | H275Y | Catalytic site | 150.0 | 19.0 | 1.0 | 2.2 | 5 |
| DS4‐371 | H275Y | Catalytic site | 130.0 | 12.0 | 0.8 | 2.3 | |||
| 2015‐2016 | DS6‐15 | D199N | Catalytic site | 1.2 | 0.6 | 2.5 | 2.4 | 24 | |
| DS6‐352 | H275Y | Catalytic site | 150.0 | 10.0 | 1.3 | 3.9 | |||
| DS6‐528 | H275Y | Catalytic site | 130.0 | 17.0 | 1.2 | 2.7 | |||
| 2016‐2017 | None | ||||||||
| A/H3N2 | 2011‐2012 | None | |||||||
| 2012‐2013 | DS3‐369 | K249E | 1.2 | 0.9 | 2.9 | 3.6 | 6 | ||
| DS3‐173 | S331R | 1.2 | 0.7 | 2.7 | 3.9 | 26 | |||
| 2013‐2014 | None | ||||||||
| 2014‐2015 | DS5‐388 | G320E | 0.9 | 0.6 | 2.2 | 2.8 | 26 | ||
| 2015‐2016 | DS6‐11 | S331R | 0.8 | 0.3 | 2.3 | 2.9 | |||
| 2016‐2017 | DS7‐129 | D151E | Catalytic site | 1.1 | 0.8 | 2.3 | 4.8 | 25 | |
| B | 2013‐2014 | None | |||||||
| 2014‐2015 | None | ||||||||
| 2015‐2016 | None | ||||||||
| 2016‐2017 | DS7‐219 | I262T | 14 | 2.1 | 7.1 | 16 | 6 | ||
AA, amino acid; HRI, highly reduced inhibition; IC50, 50% inhibitory concentration; NA, neuraminidase; NAIs, neuraminidase inhibitors; RI, reduced inhibition.
RI/HRI‐related AA mutations were extracted from NA sequencing data examined in this study, based on the previous reports.
The AA position numberings of A/H1N1pdm09, A/H3N2, and B viruses are based on N1, N2, and B type‐specific numbering, respectively.
Median IC50 values and fold changes are shown in Tables S1‐S13.