Volume 30, Number 7—July 2024
Dispatch
Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023–February 2024
Table 2
Antiviral susceptibility of available influenza A(H1N1)pdm09 virus isolates with NA-I223V or NA-S247N or NA-I223V + S247N substitutions*
| NA substitution† | No. virus isolates tested | NA inhibitors IC50, nM, average ± SD (fold)‡ |
CEN inhibitor baloxavir EC50, nM, average ± SD (fold)§ | |||
|---|---|---|---|---|---|---|
| Oseltamivir | Zanamivir | Peramivir | Laninamivir | |||
| Test viruses | ||||||
| I223V | 9 | 0.71 ± 0.17 (3) | 0.23 ± 0.03 (1) | 0.08 ± 0.01 (1) | 0.25 ± 0.01 (1) | 1.15 ± 0.15 (2) |
| S247N | 6 | 0.82 ± 0.16 (4) | 0.34 ± 0.05 (2) | 0.19 ± 0.01 (3) | 0.55 ± 0.03 (3) | 1.46 ± 0.62 (2) |
| I223V + S247N |
6 |
2.71 ± 0.20 (13) |
0.49 ±0.02 (3) |
0.29 ± 0.01 (4) |
0.64 ± 0.02 (3) |
0.67 ± 0.14 (1) |
| Reference | ||||||
| Median IC50/EC50 2022–2023 | 253 | 0.21 | 0.19 | 0.07 | 0.21 | 0.70 |
*Next-generation sequencing–flagged influenza A(H1N1)pdm09 viruses were propagated in MDCK-SIAT1 cells, followed by sequence confirmation of virus isolates. Susceptibility of available virus isolates with indicated single or dual NA substitution(s) were tested for NA inhibitors (oseltamivir, zanamivir, peramivir, and laninamivir) by using Centers for Disease Control and Prevention–standardized fluorescence-based NA inhibition assay and baloxavir by using a cell-based Influenza replication inhibition neuraminidase-based assay. Virus isolates were tested against each antiviral in at least 2–3 independent tests, and average ± SD of IC50s/EC50s is shown. Fold changes in IC50s/EC50s of test viruses were calculated compared with median IC50s/EC50s of influenza A(H1N1)pdm09 viruses tested during the 2022–23 influenza season (October 1, 2022–September 30, 2023). CEN, cap-dependent endonuclease; EC50, 50% effective concentration; IC50, 50% inhibitory concentration; NA, neuraminidase. †According to a subtype-specific NA amino acid numbering system. ‡Fold changes were interpreted according to World Health Organization classification criteria for type A: <10-fold, normal inhibition; 10–100-fold, reduced inhibition; >100-fold, highly reduced inhibition. §Fold changes were interpreted according to arbitrary criteria, according to which >3-fold increase in EC50 of test virus compared with reference EC50 is defined as reduced susceptibility to baloxavir.
1These authors contributed equally to this article.