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J Med Virol
. 2026 Jan;98(1):e70796.
doi: 10.1002/jmv.70796. Integrated Phenotypic-Genotypic Surveillance of Neuraminidase Inhibitor Susceptibility in Influenza A(H1N1), A(H3N2), and B/Victoria Viruses in Saudi Arabia, 2024-2025
Asif Naeem 1 , Maymunah Hakami 1 , Haya Aljami 1 , Haneen S Almiqbel 1 , Nabeel Alzahrani 1 , Sameera Aljohani 1 , Mohammed Bosaeed 1
Affiliations
Contemporary neuraminidase inhibitor (NAI) surveillance data from the Middle East are limited. We profiled current-season susceptibility among influenza A(H1N1), A(H3N2), and B/Victoria viruses circulating in Saudi Arabia (2024-2025) using paired phenotypic and genotypic methods. Respiratory specimens underwent virus isolation and neuraminidase-inhibition testing with the NA-XTD™ chemiluminescent assay kit (Applied Biosystems/Thermo Fisher) against oseltamivir, zanamivir, and peramivir. Half-maximal inhibitory concentrations (IC₅₀) were estimated by 4-parameter logistic models with per-plate normalization. Neuraminidase (NA) genes were Sanger-sequenced and placed within contemporaneous global lineages. Exposure margins were approximated as Cmax/IC₅₀ ratios using published clinical pharmacokinetic Cmax values. Of 240 specimens, 93 isolates were recovered: A(H1N1) (n = 61), A(H3N2) (n = 15), and influenza B virus (n = 17). In A(H1N1), S247N (7/61, 11.5%) and S200N (61/61, 100%) were associated with modest oseltamivir IC₅₀ increases versus subtype wild-type (WT) anchors; H275Y was not detected. A(H3N2) isolates lacked WHO-listed reduced-susceptibility markers overall; a single S331R isolate showed only a small right-shift, and geometric-mean IC₅₀ values for all three NAIs remained close to WT. In influenza B virus, several framework/interface substitutions were observed including F103L and I459V accompanying a subtype-specific elevation of oseltamivir IC₅₀ (B vs A geometric-mean ratio ≈20×), while zanamivir and peramivir remained comparatively potent. Across subtypes, Cmax/IC₅₀ analyses showed the widest exposure margins for peramivir, intermediate for zanamivir, and the narrowest for oseltamivir in influenza B. Phylogenies interleaved Saudi isolates within global clades without evidence of clonal expansion of reduced-susceptibility variants. During 2024-2025, influenza A viruses in Saudi Arabia remained broadly susceptible to NAIs. Influenza B virus displayed a reproducible oseltamivir right-shift linked to non-canonical framework/interface substitutions, whereas zanamivir and especially peramivir retained activity. These findings support ongoing integrated phenotype-genotype surveillance and consideration of peramivir when influenza B circulation is substantial.
Keywords: Saudi Arabia; influenza; neuraminidase inhibitors; oseltamivir; peramivir; resistance surveillance; zanamivir.
. 2026 Jan;98(1):e70796.
doi: 10.1002/jmv.70796. Integrated Phenotypic-Genotypic Surveillance of Neuraminidase Inhibitor Susceptibility in Influenza A(H1N1), A(H3N2), and B/Victoria Viruses in Saudi Arabia, 2024-2025
Asif Naeem 1 , Maymunah Hakami 1 , Haya Aljami 1 , Haneen S Almiqbel 1 , Nabeel Alzahrani 1 , Sameera Aljohani 1 , Mohammed Bosaeed 1
Affiliations
- PMID: 41527997
- DOI: 10.1002/jmv.70796
Contemporary neuraminidase inhibitor (NAI) surveillance data from the Middle East are limited. We profiled current-season susceptibility among influenza A(H1N1), A(H3N2), and B/Victoria viruses circulating in Saudi Arabia (2024-2025) using paired phenotypic and genotypic methods. Respiratory specimens underwent virus isolation and neuraminidase-inhibition testing with the NA-XTD™ chemiluminescent assay kit (Applied Biosystems/Thermo Fisher) against oseltamivir, zanamivir, and peramivir. Half-maximal inhibitory concentrations (IC₅₀) were estimated by 4-parameter logistic models with per-plate normalization. Neuraminidase (NA) genes were Sanger-sequenced and placed within contemporaneous global lineages. Exposure margins were approximated as Cmax/IC₅₀ ratios using published clinical pharmacokinetic Cmax values. Of 240 specimens, 93 isolates were recovered: A(H1N1) (n = 61), A(H3N2) (n = 15), and influenza B virus (n = 17). In A(H1N1), S247N (7/61, 11.5%) and S200N (61/61, 100%) were associated with modest oseltamivir IC₅₀ increases versus subtype wild-type (WT) anchors; H275Y was not detected. A(H3N2) isolates lacked WHO-listed reduced-susceptibility markers overall; a single S331R isolate showed only a small right-shift, and geometric-mean IC₅₀ values for all three NAIs remained close to WT. In influenza B virus, several framework/interface substitutions were observed including F103L and I459V accompanying a subtype-specific elevation of oseltamivir IC₅₀ (B vs A geometric-mean ratio ≈20×), while zanamivir and peramivir remained comparatively potent. Across subtypes, Cmax/IC₅₀ analyses showed the widest exposure margins for peramivir, intermediate for zanamivir, and the narrowest for oseltamivir in influenza B. Phylogenies interleaved Saudi isolates within global clades without evidence of clonal expansion of reduced-susceptibility variants. During 2024-2025, influenza A viruses in Saudi Arabia remained broadly susceptible to NAIs. Influenza B virus displayed a reproducible oseltamivir right-shift linked to non-canonical framework/interface substitutions, whereas zanamivir and especially peramivir retained activity. These findings support ongoing integrated phenotype-genotype surveillance and consideration of peramivir when influenza B circulation is substantial.
Keywords: Saudi Arabia; influenza; neuraminidase inhibitors; oseltamivir; peramivir; resistance surveillance; zanamivir.