#Report on #influenza viruses received and tested by the #Melbourne #WHO Collaborating Centre for Reference and Research on Influenza during 2025

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne (the Centre) received 13,817 human influenza-positive samples during 2025. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. Of the 13,817 samples received or processed, influenza A(H1N1)pdm09 viruses predominated, accounting for 46.1% of samples, compared to 21.2% for A(H3N2) viruses and 19.5% for influenza B viruses; one influenza C virus was received. Among viruses analysed at the Centre, the majority of A(H1N1)pdm09 (> 99%) and influenza B (98%) viruses were antigenically similar to their respective WHO recommended vaccine strains for the Southern Hemisphere in 2025. In contrast, only 43% of A(H3N2) viruses were antigenically similar to their respective WHO recommended vaccine strains. Of 3,307 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, 37 A(H1N1)pdm09 viruses showed highly reduced inhibition by oseltamivir and no influenza viruses tested showed highly reduced inhibition by zanamivir. Of 5,080 samples with sequencing of the polymerase acidic (PA) gene, no genetic markers associated with highly reduced susceptibility to baloxavir marboxil were identified.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3489

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COMbination #therapy with #baloxavir and #oseltamivir 1 for hospitalized patients with #influenza: The pragmatic COMBO 1 randomized controlled trial

 

Abstract

Background

COMBO 1 compared time to cessation of viral shedding (TCVS) among hospitalized influenza patients treated with oseltamivir plus a single dose of baloxavir vs. oseltamivir alone.

Methods

In a quadruple-blinded, placebo-controlled parallel group multicenter randomized controlled trial, hospitalized patients with laboratory-confirmed influenza were randomly enrolled in a 1:1 ratio to Group 1 (oseltamivir+placebo) or Group 2 (oseltamivir+baloxavir). All patients were treated with oseltamivir for 5 days; one dose of baloxavir or placebo was given in identical capsules. Primary efficacy and safety outcomes were TCVS by virus titer with qCulture TCID50 agglutination and 30-day severe adverse event (SAE) rate, respectively. Secondary virology, clinical, and safety outcomes were assessed. Continuous and categorical data were analyzed with Wilcoxon Rank-Sum and Fisher’s Exact Tests, respectively.

Results

14 participants were randomized and received study drug (Group 1: n=6, Group 2: n=8); the study was stopped early due to slow accrual. Baseline characteristics were balanced. Median TCVS with qCulture was 53.3 hours in Group 1 and 25.3 hours in Group 2 (p=0.13). 30-day overall SAE rates were 16.7% and 12.5%, respectively. All patients achieved negative qCulture. Median TCVS with quantitative PCR (RT-qPCR) was 115.6 and 34.4 hours (p=0.24); % achieving viral negative by RT-qPCR was 33.3% and 75.0% (p=0.28), respectively.

Conclusions

Combination therapy with oseltamivir and a single dose of baloxavir was inconclusive with non-significant trends towards shorter median TCVS vs. monotherapy with oseltamivir in hospitalized patients with influenza. Interpretation is limited by small sample size and early termination.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/13596535261479944

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A randomised, open-label clinical study on the efficacy of #baloxavir marboxil and #oseltamivir for post-exposure #prevention of #influenza in a #hospital setting: a study protocol

 

Abstract

Introduction 

Healthcare settings are high-risk environments for the transmission of respiratory viruses. Effective strategies to prevent hospital-acquired influenza, particularly post-exposure prophylaxis for close contacts (CCs), are urgently needed. This study aims to assess the effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in preventing influenza virus infection among CCs who have been exposed to confirmed influenza cases and are unable to be immediately isolated in the hospital ward.

Methods and analysis 

This multicentre, randomised, open-label, parallel-controlled trial involves hospitalised patients with laboratory-confirmed influenza (index patients) and their CCs. CCs will be randomised into three groups: baloxavir marboxil, oseltamivir or placebo. Baloxavir (40 mg or 80 mg for ≥80 kg) will be administered as a single dose on day 1, while oseltamivir (75 mg) will be given once a day for 5 days. CCs will be monitored for influenza-like symptoms, with respiratory samples collected for rapid antigen test or reverse-transcription PCR testing at baseline, day 5±1 and day 10±1 or earlier if symptoms develop. The primary outcome is the 5-day incidence of clinical influenza, defined as laboratory-confirmed infection with concurrent fever and at least one respiratory symptom. Secondary outcomes will include the 5-day incidence of laboratory-confirmed influenza, the 10-day incidence of clinical influenza and the percentage of CCs infected with resistance-associated treatment-emergent influenza variants.

Ethics and dissemination 

The study has been approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2024-KY-401). The results of the study will be submitted for publication in a peer-reviewed journal with online accessibility. The full protocol, de-identified participant data and statistical code will be openly available in a public repository within 12 months after trial completion.

Trial registration number NCT06762587. 

https://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.

Source: 

Link: https://bmjopen.bmj.com/content/16/8/e118748

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The association of empirical #treatment with #oseltamivir with the #outcome of critically ill patients admitted with severe acute respiratory illness (#SARI)

 

Abstract

Objective

Neuraminidase inhibitors (NAIs) are widely used empirically in critically ill patients with suspected influenza; however, their effect on mortality remains uncertain. This multicenter study evaluates the association between empirical treatment with oseltamivir and the outcome of critically ill patients with Severe Acute Respiratory Infection (SARI) admitted to the Intensive Care Unit (ICU).

Methods

This was a retrospective cohort study conducted in the ICUs of four hospitals in Saudi Arabia, involving adult patients with SARI from September 2012 to December 2018. Data collected were: demographics, comorbidities, clinical presentation, and outcomes among patients treated with oseltamivir and those who were not. The primary outcome was 90-day mortality. The association of oseltamivir and mortality was evaluated adjusting for propensity score.

Results

During the study period, 456 patients with SARI were included in the study, 301 were treated with empirical oseltamivir within a median of 1 day from presentation (interquartile range, 0-1 day) and a median of 4 days after symptom onset, while 155 patients were not. No significant differences were observed in baseline characteristics between the two groups. Of the included patients, 334 (73%) were tested for influenza using PCR, and 87 (26%) had a confirmed diagnosis of influenza. Patients on oseltamivir were less likely to require rescue oxygen therapy (22.9% vs. 34.8%, p=0.007), and had shorter hospital stay (20 days vs. 27 days, p=0.01). Patients treated with oseltamivir had significantly reduced 90-day mortality on adjusted analyses (aOR: 0.87, 95% CI: 0.81-0.94, p=0.0002). Subgroup analysis revealed that the association with reduced mortality extends to patients >70 years old (aOR: 0.94, 95% CI: 0.89-0.99, p=0.02) and those with negative influenza tests (aOR: 0.81, 95% CI: 0.79, 0.84, p<0.0001).

Conclusion

Among critically ill patients with SARI, empirical treatment with oseltamivir was associated with lower mortality. These results add to the body of evidence suggesting clinical benefits of oseltamivir in managing critically ill patients with influenza-like illnesses.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/20503121261478401

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Effectiveness of #Oseltamivir in Hospitalized #Children With Laboratory-Confirmed #Influenza, 2014-2023

 

Key Points

    ° Question: 

        § Does oseltamivir treatment reduce risk of intensive care unit (ICU) admission and hospital length of stay among pediatric patients hospitalized with influenza?

    ° Findings:  

        § Using a cohort study from a population-based surveillance network in 13 states across 8 influenza seasons, oseltamivir treatment was found to decrease both the likelihood of ICU admission and hospital length of stay among pediatric patients hospitalized with laboratory-confirmed influenza.

    ° Meaning:  

        § These findings support the current national recommendations from the American Academy of Pediatrics, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America that recommend antiviral treatment for children hospitalized with laboratory-confirmed influenza.

Abstract

Importance  

National organizations recommend antiviral treatment for hospitalized children with influenza; however, use in this setting has recently declined. Studies of oseltamivir effectiveness in children are limited by misclassification bias, unknown symptom onset date, and incomplete capture of antiviral use prior to admission.

Objective  

To assess the association between oseltamivir receipt and intensive care unit (ICU) admission and hospital length of stay (LOS) among pediatric influenza-associated hospitalizations.

Design, Setting, and Participants  

This cohort study used data that were obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET), which conducts US population-based surveillance for laboratory-confirmed influenza hospitalizations for all ages across 13 states. The study data include seasons 2014 to 2015 through 2022 to 2023, excluding 2020 to 2021. Participants included children aged younger than 18 years who were hospitalized with laboratory-confirmed influenza and for whom a respiratory symptom onset date was available. These data were analyzed from October 2024 through May 2026.

Exposures  

Oseltamivir receipt as a time-dependent exposure.

Main Outcome(s) and Measure(s)  

The primary outcome was time from symptom onset to ICU admission. Secondary outcome was time from admission to discharge (LOS). Adjusted Cox proportional hazard models (aHR) with oseltamivir receipt as a time-dependent exposure were used.

Results  

After exclusions, 6044 influenza cases were included in the primary ICU analysis, of whom 4240 (70.2%) received oseltamivir, and 7103 cases were included in the secondary LOS analysis, of whom 5746 (80.9%) received oseltamivir. In the ICU analysis, the median (IQR) age was 3 (1-7) years, 3382 (56%) were male and 3721 (44%) were female, and 2937 (49%) had 1 or more medical comorbidity—the most common of which was asthma in 1547 children (26%). In adjusted models, compared with untreated children, oseltamivir treatment reduced the hazard of ICU admission (aHR, 0.69; 95% CI, 0.60-0.80) and shortened LOS (analyzed as hazard of hospital discharge; aHR, 1.13; 95% CI, 1.06-1.21).

Conclusions and Relevance  

In this cohort of children hospitalized with influenza, oseltamivir treatment was significantly associated with a reduced risk of ICU admission by 31% and decreased hospital LOS. These findings demonstrate the benefits of oseltamivir receipt and support current national recommendations for oseltamivir treatment as soon as possible in children hospitalized with suspected or laboratory-confirmed influenza.

Source: 

Link: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2852671

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Detection and characterization of #antiviral #resistant viruses during the #influenza season of 2024–25

 

ABSTRACT

During the high severity season of 2024–25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01514-26

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#Baloxavir, #favipiravir, or #oseltamivir in patients with non-severe symptomatic seasonal #influenza (AD ASTRA): a phase 2, open-label, adaptive, RCT

 

Summary

Background

The oral antiviral therapies baloxavir marboxil (hereafter baloxavir), favipiravir, and oseltamivir have not been simultaneously compared for the treatment of seasonal influenza. We aimed to determine their relative efficacies in accelerating viral clearance in patients with symptomatic influenza virus infection at low risk of progression to severe disease.

Methods

We conducted a phase 2, open-label, randomised, controlled, adaptive platform trial in patients aged 18–60 years in Thailand, Laos, Nepal, and Brazil, recruited in four hospital outpatient or primary care departments with acute influenza (≤ 4 days of symptoms) and a low risk of progression to severe disease. Patients were randomly assigned 1:1:1:1:1 using a centralised online app to receive baloxavir (single oral dose of 40 mg if bodyweight <80 kg or 80 mg if bodyweight ≥80 kg), favipiravir (oral loading dose of 1800 mg, followed by 1800 mg 12 h later, and then 800 mg twice daily for 4 days), oseltamivir (oral dose 75 mg twice daily for 5 days), no study drug, or another ongoing intervention (reported separately). Randomisation was stratified by site and used block sizes of 15. The primary endpoint was the rate of oropharyngeal influenza viral RNA clearance, estimated under a Bayesian hierarchical linear model fitted to the daily log10 oropharyngeal viral densities from day 0 to day 5. Analyses were conducted in the modified intention-to-treat population (mITT), defined as patients with PCR-confirmed influenza with more than 250 viral RNA copies per mL at randomisation. Intervention groups were assessed for superiority over the no study drug group (posterior probability >0·9 that the relative increase in viral clearance was ≥20%); if superiority was met, intervention groups were assessed for non-inferiority relative to baloxavir (posterior probability >0·9 that the relative reduction in viral clearance was ≤10%). Secondary outcomes included time to resolution of fever and time to resolution of all symptoms. The trial is registered with ClinicalTrials.gov (NCT05648448) and is ongoing.

Findings

Between Feb 22, 2023, and Dec 12, 2025, 944 patients with influenza virus infection were randomly assigned to baloxavir (n=199; mITT 163 [82%]), favipiravir (n=223; mITT 196 [88%]), oseltamivir (n=200; mITT 170 [85%]), no study drug (n=228; mITT 200 [88%]) or other interventions (n=94). 120 patients were excluded based on baseline viral density (≤250 copies per mL), and one participant withdrew before collection of quantitative PCR results on day 0. 457 (63%) patients in the mITT population were female and 272 (37%) were male. Compared with no study drug, viral clearance rates were accelerated by 86% (95% credible interval [CrI] 60–117) with baloxavir, 66% (45–94) with favipiravir, and 49% (28–74) with oseltamivir. For all interventions, the posterior probability that the relative increase in viral clearance was 20% or more was 1·0. Compared with baloxavir, oseltamivir was inferior (20% slower clearance, 95% CrI 6 to 32; posterior probability 0·93 that the relative reduction in viral clearance was <10%); non-inferiority could not be shown for favipiravir (10% slower clearance, 95% CrI –4 to 22; posterior probability 0·55 that the relative reduction in viral clearance was <10%). Median time to fever resolution was accelerated with all three antivirals compared with no study drug (absolute differences ranging from 0·5 days to 0·9 days), whereas time to resolution of all symptoms was not significantly different between groups. 31 adverse events of grade 3 or above occurred, five of which were considered severe (one in the favipiravir group, one in the oseltamivir group, and three in the no study drug group).

Interpretation

Oral baloxavir, favipiravir, and oseltamivir accelerated influenza viral clearance rates in adults with early non-severe seasonal influenza at low risk of progression to severe disease. Baloxavir had the greatest in-vivo antiviral efficacy, followed by favipiravir and oseltamivir. These antivirals shortened fever duration but showed no clear effects on time to complete symptom resolution. This pharmacometric approach can inform prioritisation of antiviral agents for further study and potential inclusion in pandemic stockpiles.

Funding

Wellcome Trust.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00255-0/fulltext

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#Mutations in severe #human #H5N1 cases facilitate #evasion from human mucus and #antivirals

 

Abstract

In late 2024, two individuals in Canada and the United States were treated in intensive care for acute respiratory distress caused by infection with the avian Influenza A Virus H5N1 2.3.4.4b genotype D1.1. Viral sequence data obtained from sampling these patients indicated mixed alleles at haemagglutinin (HA) positions 190 and 226. Mutations at these positions are key determinants of HA usage of α2,6-linked sialic acids (SA), the most abundant influenza receptors in human upper respiratory tracts. Thus, these mutations raised concerns about human adaptation and pandemic potential of the H5N1 virus. In this study, we investigated the impact of the mutations at residues 190 and 226 in H5 HA. We studied the receptor binding properties, cell entry phenotypes and fitness impacts of the mutations using recombinant proteins, pseudotyped lentiviruses, and in the context of influenza viruses using reverse genetics. The mutations did not confer any detectable α2,6-linked sialic acid receptor usage either alone or in combination. Rather, viruses carrying these mutations exhibit weakened binding towards α2,3-linked sialic acid receptors. This correlated with an enhanced capacity to evade human airway mucus, and a reduced susceptibility to oseltamivir and zanamivir. This research underscores that in addition to the way HA interacts with SA as entry receptors, other factors that impact the HA/NA balance might influence the evolutionary trajectory of a zoonotic virus in the human respiratory tract. This study presents a new paradigm for the evolutionary drivers of HA, where reduced sialic acid binding can serve as an advantage for escape from host barriers and antivirals.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MR/Y015061/1, CC2127

Biotechnology and Biological Sciences Research Council, BB/Y007298/1, APP104179, BBS/E/PI/23NB000, BBS/E/PI/23NB0003

Wellcome Trust, https://ror.org/029chgv08, CC2127, 218304/Z/19/Z

Department for Environment Food and Rural Affairs, BB/Y007298/1

The Pirbright Institute, BBS/E/PI/230002A, BBS/E/PI/230001C, BBS/E/PI/230002B

Cancer Research UK, CC2127

UK Research and Innovation, https://ror.org/001aqnf71, UKRI3602

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.28.740943v1

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#Oseltamivir #Resistance in #Human #Influenza #H5N1 and #H7N9 Infections: A Mini Review

 

Abstract

Avian influenza viruses (AIVs) have been reported to cause infections in humans following avian-to-human transmission, resulting in a range of clinical outcomes. A(H5N1) and A(H7N9) infections, which constitute the majority of human AIV cases, are responsible for severe infections leading to high mortality. The neuraminidase inhibitor oseltamivir is expected to play a major role for the control of AIV infections in humans. However, the emergence of resistance may compromise the impact of antiviral therapy. The objective of this article is to review human cases of A(H5N1) and A(H7N9) infections for which mutations of oseltamivir resistance were detected. Neuraminidase mutations rapidly occurred in a subtype-specific manner, with H274Y and N294S substitutions predominating in A(H5N1) cases and the R292K substitution in A(H7N9) cases. Serious clinical outcomes and mortality were seen in most A(H5N1) and A(H7N9) cases despite oseltamivir therapy, thus highlighting the need for improving antiviral strategies against these AIVs.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag393/8722865

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Characterization of #oseltamivir-resistant #H5N1 clade 2.3.4.4b, genotype #D1.1 #variants identified in #poultry farms of British Columbia, #Canada

 

ABSTRACT

Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b, genotype D1.1, are responsible for widespread outbreaks in poultry and continue to cause sporadic, sometimes severe, human infections. Herein, we characterized a wild-type (WT) influenza A(H5N1) D1.1 isolate (BC-H5N1-WT) and its H275Y neuraminidase (NA) variant (BC-H5N1-H275Y), both of which emerged on farms in British Columbia, Canada, during the fall 2024 outbreak. In vitro analysis assessed replication kinetics in MDCK cells, with supernatants collected at different days post-infection (p.i.) and titrated by TCID50 and qRT-PCR. Neuraminidase inhibitor (NAI) susceptibility was determined by NA inhibition assays, whereas susceptibility to baloxavir acid (BXA) was evaluated by plaque reduction assay. In vivo virulence was evaluated in BALB/c mice infected with serial 10-fold dilutions of each virus to monitor weight loss and mortality. Viral titers in lungs, brain, nose, kidney, spleen, and heart were quantified at day 4 p.i. The BC-H5N1-WT virus was susceptible to the four antivirals tested, whereas BC-H5N1-H275Y displayed resistance to oseltamivir and peramivir but remained susceptible to zanamivir and BXA. The BC-H5N1-WT exhibited significantly higher viral replication titers than BC-H5N1-H275Y at all tested time points and showed larger plaque sizes. In mice, BC-H5N1-WT was more virulent with LD50 values of 1.78 × 103 PFUs compared to 8.71 × 104 PFUs for BC-H5N1-H275Y, and produced higher viral titers in lungs and other organs. Despite the reduced fitness of the resistant H5N1 D1.1 variant, its emergence in the absence of viral selection pressure underscores the need for continued surveillance.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2686474

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First #Ecuadorian #Pediatric Case of Multisystem and #Neurological Involvement Associated with #Influenza A #H5N1 Virus—Case Report

 

Abstract

Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry. The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock. Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state. Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival. Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/749

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Evaluation of #antiviral #treatments for highly pathogenic avian #influenza virus #infections in #feline species

 

Abstract

In 2020, highly pathogenic avian influenza (HPAI) isolates from clade 2.3.4.4b emerged in Europe and spread globally, including in bovine hosts in the USA. Viruses from this clade cause minimal disease in dairy cattle, characterized by decreased milk production but low mortality rates. Infections have also occurred in feline hosts. In contrast to cows, infection of cats (and closely related species, including skunks and foxes) can result in severe neurological signs and mortality. Documented feline H5N1 infections from clade 2.3.4.4.b have a mortality rate of approximately 80% following rapid onset of clinical signs. No antiviral compounds have been tested in an experimental feline model; however, anecdotal clinical evidence suggests early treatment with oseltamivir may improve outcomes in felines with HPAI. Here, we show the in vitro efficacy of several influenza inhibitors in feline glial astrocyte (PG-4) and kidney (CRFK) cell culture models using the clade 2.3.4.4.b virus Tx2/24 (H5N1). The neuraminidase inhibitor oseltamivir carboxylate did not effectively inhibit viral replication in either cell line. The cap-dependent endonuclease inhibitor baloxavir exhibited the strongest inhibition of this virus, with EC50 values of 30 nM in PG-4 and 1 μM in CRFK cells. Amantadine and rimantadine, M2 ion channel inhibitors, were unable to completely inhibit viral replication in either cell line at any concentration utilized. The broad-spectrum nucleoside analog GS-441524 demonstrated little to no inhibition of viral replication in either cell line. Additionally, the mutagenic NHC analogs EIDD-1931 and EIDD-2801 successfully inhibited viral replication at the maximum tested concentration of 100 μM but exhibited significant cytotoxicity. Our findings suggest that baloxavir should be considered by veterinary clinicians as the first-line drug of choice when presented with felines or other species infected with HPAI.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Cornell Feline Health Center, Ithaca, US

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.06.09.730954v1

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A mouse #model of #human-derived #H10N3 #influenza enables preclinical evaluation of #antiviral efficacy

 

Highlights

• Revealing one human-derived H10N3 virus was highly lethal to C57BL/6J, ICR, and BALB/c mice;

• Successfully establishing the first human-derived H10N3-infected mice model.

• In vitro antiviral assay revealed that this human-origin H10N3 virus exhibits natural resistance to oseltamivir, but remains sensitive to peramivir and baloxavir.

• Oseltamivir or BM immediate treatment after infection effectively prevented mortality caused by H10N3,but their efficacy with a 24h delay were significantly weaker than that of peramivir.

• BM one-dose treatment with a 24h delay has no protective effect, but BM combination with NAIs exhibits significant additive effect on mortality caused by H10N3.

• BM and NAIs combination may be a promising therapy for combating novel H10N3 virus infection.

Abstract

    Human infections with avian influenza A (H10N3) have recently been reported, representing a notable global public health concern. To seek effective strategies for emerging H10N3 virus infection and provide tools for vaccine and antiviral drugs development, we established a mouse model with a novel human-derived H10N3 virus. Our findings revealed that this human-derived H10N3 virus was highly lethal to C57BL/6J, ICR, and BALB/c mice. Neuraminidase inhibitors (oseltamivir or peramivir) effectively conferred protection for H10N3 low-lethal infection, but the efficacy of peramivir is superior to that of oseltamivir. One single dose of baloxavir marboxil (BM) treatment at 2 h post-infection provides complete protection against mortality, but BM treatment with a 24h delay has no protective effect against mortality caused by H10N3 virus infection. Furthermore, BM multiple doses treatment with a 24h delay for H10N3 infection remains effective in preventing weight loss and enhancing viral clearance, but its protective efficacy against mortality was significantly attenuated. However, both in vitro and in vivo combination of BM with NAIs exhibit significant additive effect against H10N3 virus infection than BM or NAIs monotherapy. Our findings suggest that combination of BM with NAIs represents a promising therapeutic strategy for emerging H10N3 infections in clinical practice.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226000951?via%3Dihub

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#Antiviral treatment for #influenza

 

Abstract

Seasonal influenza is a widespread acute respiratory infection that causes significant illness and death worldwide. Two major antiviral classes are neuraminidase inhibitors (NAIs) and polymerase inhibitors. NAIs, including oseltamivir, zanamivir, peramivir and laninamivir, block viral release, while polymerase inhibitors such as baloxavir disrupt viral RNA replication. Early administration within 48 h of symptom onset reduces illness duration, severity and complications, particularly in high-risk groups. Oseltamivir is the most widely studied NAI, demonstrating reduced viral shedding, faster symptom resolution and lower complication rates, though gastrointestinal side effects are common. Higher doses generally do not improve outcomes compared to standard dosing. Zanamivir is more effective against influenza B and is inhibitory for most influenza A viruses resistant to oseltamivir, but the inhaled formulation is less suitable for patients with severe illness or airway disease. Intravenous (IV) zanamivir is approved for hospitalized influenza patients in some countries. Peramivir offers IV treatment options, while laninamivir is mainly used in Japan. Baloxavir shows superior viral load reduction and comparable symptom relief to oseltamivir in outpatients, though resistance variants can emerge. Favipiravir and newer polymerase inhibitors are under investigation. Combination therapies may enhance recovery, with limited evidence. Overall, timely antiviral use is critical to reducing influenza’s burden.

This article is part of the Theo Murphy meeting issue ‘Evaluating anti-infective drugs’.

Source: 

Link: https://royalsocietypublishing.org/rstb/article/381/1949/20240344/481548/Antiviral-treatment-for-influenza

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#Genetic and #biological characterization of a #duck-origin clade 2.3.4.4b #H5N6 avian #influenza virus reveals partial #mammalian #adaptation

 

Highlights

• Duck-origin H5N6 virus A/Duck/Jiangsu/628/2022 shares high homology with the human strain A/Yangzhou/125/2022.

• The 628 strain shows mammalian adaptation markers: HA mutations enhance human receptors affinity and NA mutations reduce sensitivity to neuraminidase inhibitors.

• Limited airborne transmission but detectable droplet-mediated spread suggests increased mammalian transmission risk.

Abstract

Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S037811352600146X?via%3Dihub

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Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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Prompt and Intensive #Antiviral #Chemoprophylaxis in Nursing Home #Influenza #Outbreaks

 

Key Points

-- Question:  Is initiation of antiviral chemoprophylaxis with oseltamivir for 70% or more of eligible nursing home (NH) residents within 2 days of outbreak detection associated with lower 14-day and 30-day mortality and hospitalization compared with a nonintensive approach?

-- Findings:  In this cohort study of 404 influenza outbreaks across 318 NHs with 35 086 resident-trial observations using a sequential target trial emulation and the randomize-censor-weight approach, hospitalization but not death was lower at 14 days post outbreak in NHs that implemented intensive antiviral chemoprophylaxis; 30-day estimates were directionally similar but less precise.

-- Meaning:  Results of this study suggest that clinicians should promptly initiate antiviral chemoprophylaxis in at least 70% of NH residents within 2 days of an influenza outbreak to markedly reduce influenza-related hospitalizations.

Abstract

Importance  

Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear.

Objective  

To examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

Design, Setting, and Participants  

Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018–May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.

Exposures  

Intensive antiviral chemoprophylaxis with oseltamivir (≥70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Main Outcomes and Measures  

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Results  

Among 404 outbreaks in 318 NHs, 35 086 resident-trial observations (29 683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17 155 observations; 17 931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of –0.06% (95% CI, −0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of –0.96% (95% CI, −1.78% to −0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.

Conclusions and Relevance  

Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

Source: 

Link: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2846967

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Use of #baloxavir as adjunctive #antiviral #therapy to neuraminidase inhibitors in severely immunocompromised individuals infected with #influenza

 

ABSTRACT

Immunocompromised patients are at risk of developing severe influenza, with protracted viral shedding and development of resistance-associated mutations under antiviral treatment. We report a case series of severely immunocompromised hematology patients, including allogeneic hematopoietic cell transplantation (HCT) recipients, treated with both baloxavir and oseltamivir and describe clinical and virological outcomes and the safety profile of prolonged combination therapy. Allogeneic HCT recipients with influenza infection treated with baloxavir were retrieved via institutional databases. All hospitalized allogeneic HCT patients treated with a combination therapy of baloxavir and oseltamivir over five influenza seasons between October 2019 and May 2025 were included. Six influenza-infected hematology patients (5/6 allogeneic HCT recipients) were treated with combination therapy of oseltamivir and baloxavir. All patients presented with lower respiratory tract infections. Oseltamivir treatment duration ranged from 5 to 31 days, and the number of administered baloxavir doses ranged between one and five. Baloxavir administration was well tolerated, and no adverse events could be attributed to the administered antiviral treatment. All-cause mortality at 3 months post-infection was 66% (4/6), mainly driven by underlying disease. In two patients with protracted shedding, combination therapy did not prevent the development of resistance mutation(s). Combination treatment with prolonged courses of oseltamivir and repeated doses of baloxavir was well tolerated. No definitive conclusions on the efficacy of this approach could be drawn from this study. More data are required on the best treatment of hematology patients infected with influenza.

Source: 

Link: https://journals.asm.org/doi/10.1128/aac.01659-25

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#Oseltamivir aziridines are potent #influenza #neuraminidase #inhibitors and imaging agents

 

Significance

Influenza remains a major global health threat. We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine. This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes, selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development.

Abstract

Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals, including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir, are limited by noncovalent binding and emerging resistance. We hypothesized that Oseltamivir aziridines would unite transition-state mimicry for tight binding, with aziridine-enabled covalent capture of the catalytic tyrosine, thereby supporting both therapy and activity-based quantification. Here, we present oseltamivir-based aziridines, inspired by cyclophellitol chemistry, that act as covalent inhibitors and activity-based probes via an N-acylaziridine warhead. Free-energy calculations, and NMR observations, indicate a 4H5 half-chair preference consistent with the NA transition state, and selected analogues inhibit multiple NA subtypes with low nanomolar binding constants. Diverse evidence establishes covalency: time-dependent inactivation, inhibitor washout, intact-mass shifts, MS/MS identification of a tyrosine adduct, and QM/MM reaction profiles, while cryoEM of N1 aligns with the proposed binding mode, revealing an elimination product. The inhibitors demonstrate formidable activity against diverse viral neuraminidases, including H5N1, and further enable imaging and quantification of active NA. With their dual therapeutic and diagnostic potential, these first-in-class inhibitors indeed benefit from transition state mimicry and covalency, and thus offer a powerful platform for antiviral development and neuraminidase imaging, addressing urgent global health needs in influenza treatment and prevention.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2504045123

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14th Meeting of #WHO #Expert Working Group of the Global #Influenza #Surveillance and Response System (GISRS) for Surveillance of #Antiviral Susceptibility (March 20 '26)

Weekly epidemiological record 

20 MARCH 2026, 101th YEAR, No 12, 2026, 101, 53–56

http://www.who.int/wer 

Executive Summary 

The WHO Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (AVWG) supports the WHO GISRS by providing practical guidance for monitoring antiviral susceptibility of seasonal and emerging influenza viruses through global surveillance efforts. 

The 14th WHO-AVWG meeting was held in virtual format on 10-12 June 2025. 

Update on susceptibility of seasonal influenza viruses to approved antiviral agents 

From approximately May 2024 to May 2025, five WHO Collaborating Centres (CCs) and two National Influenza Centres (NICs) reported co-circulation of influenza A(H1N1) pdm09, A(H3N2), and B/Victoria viruses. 

A(H1N1)pdm09 dominated in Eastern Asia{1}. Elevated frequency of influenza neuraminidase (NA) inhibitor (NAI) reduced inhibition/ highly reduced inhibition (RI/HRI) was identified among A(H1N1)pdm09 viruses, largely conferred by the NA-H275Y substitution. 

Reporting frequency was 3.8% in China, lower (≤1%) in other reporting regions, but still measurable and were in some cases a result of prior antiviral use or specific local outbreaks (e.g., a hospital in Iceland with a NA-H275Y+S247N cluster, a primary school classroom outbreak in Japan{2}. The NA-S247N substitution (≤3.3%) was also noted by three centres, but these viruses exhibited normal inhibition (NI) by NAIs when available isolates were tested. 

Incidence of RI/HRI or NA-associated markers were less frequently reported for A(H3N2) and B/Victoria viruses than A(H1N1)pdm09 viruses. 

Markers and incidence of reduced susceptibility to baloxavir was detected at low frequencies of 0.07 to 2.2%, where the latter value represented a small sample set of only 2 of 89 viruses in Japan. 

Reduced susceptibility or amino acid markers indicative of reduced susceptibility were observed only in influenza A viruses and not influenza B. 

Update on susceptibility of zoonotic and animal influenza viruses  to approved antiviral agents 

From approximately May 2024 to May 2025, global surveillance data from WHO CCs, NICs, and associated partners including WHO Essential Regulatory Laboratories and the OFFLU (WOAH/FAO Network of Expertise on Animal Influenza) network reported that most zoonotic and avian influenza viruses, particularly circulating A(H5N1/x) HA clade 2.3.4.4b and 2.3.2.1a/e viruses, were broadly susceptible to NAIs and baloxavir. 

A(H5N1) 2.3.4.4b virus oseltamivir inhibitory concentrations remain elevated vs. seasonal N1 viruses. 

Small and isolated incidence of NAI associated RI/HRI or markers included: NA-D199G mediated oseltamivir/zanamivir RI detected in A(H5N1) 2.3.4.4b poultry in the Russian Federation (February 2024, reported June 2025), NA-N295S in poultry in India A(H5N1) 2.3.2.1a isolates, and 8 poultry farms in British Columbia, Canada exhibiting A(H5N1) 2.3.4.4b with NA-H275Y. 

Only two viruses with reduced baloxavir susceptibility were identified, 1 human virus with PA-I38M (California, USA) and 1 environmental virus isolate with PA-V100I (China, Hong Kong Special Administrative Region). 

Beyond A(H5N1/x), nearly 30 avian influenza subtypes including A(H9N2), A(H7N2), A(H7N7), and A(H7N9), and A(H10N7) were analysed across surveillance sites in the Bangladesh, Egypt, the Netherlands and the United States of America (USA). 

They generally lacked NA or PA genotypic markers of reduced drug susceptibility and when available for phenotypic testing, were susceptible to both NAIs and baloxavir. 

A(H7N2) and A(H7N7) viruses from the Netherlands displayed oseltamivir RI compared to human seasonal references, but this may be due to foldchange comparison to a mismatched NA subtype. 

Swine-origin variant viruses (A(H1N1)v, A(H1N2)v, A(H3N2)v) tested across the USA and Europe were largely free of genotypic or phenotypic indicators of reduced susceptibility/inhibition to NAIs or baloxavir. 

Some viruses (the  Netherlands) showed slightly higher NAI median inhibitory concentrations to historical or human seasonal baselines, but all remained below NAI RI thresholds. 

Update of protocols and guidance for GISRS laboratories 

Both genotypic and phenotypic assays may be used as tools to monitor susceptibility of influenza viruses to NAIs and baloxavir. 

The WHO-AVWG routinely reviews and updates influenza NA and PA amino acid substitutions associated with reduced susceptibility to NAIs and baloxavir; updated tables for the previous reporting period were included on the WHO website{3–5}. 

The US CDC continues to update and ship reference virus panels that can be used for NAI and baloxavir susceptibility testing, available via the International Reagent Resource{6} 

Further guidance on baloxavir and other PA inhibitor testing included the Influenza Replication Inhibition Neuraminidase-based Assay (IRINA), published by the Centers for Disease Control and Prevention, USA{7} and included on the WHO website{8}. 

The WHO AVWG continues to develop algorithms for NICs to aid in influenza response planning (zoonotic, pandemic, and antiviral resistance-specific events), guidance to aid in decisions making for testing strategies (genotypic vs. phenotypic), and guidance for consideration of baloxavir and PA inhibitor specific amino acid substitutions associated with reduced drug susceptibility{9}. 

Additionally, the WHO-AVWG has worked with GISAID to continue to refine and implement modifications to existing tools to facilitate identification of NA and PA substitutions upon sequence submission. 

Outbreak and pandemic preparedness with clinicians’ perspectives 

Two physicians, Profs. Prof. David Hui and Bin Cao, were invited to present recently updated WHO guidance on clinical practice guidelines for influenza{10}. 

Significant updates and discussion surrounded inclusion of baloxavir, which was conditionally recommended for non-severe disease high-risk patients and post-virus exposure prophylaxis (PEP) including influenza viruses associated with high mortality. 

Conditional recommendation against any NAI or baloxavir intervention remains for non-severe disease low-risk patients or seasonal virus PEP. 

Data was presented on multiple PA inhibitors rapidly moving through late-stage clinical trials in China which may have implications on expanded usage of this newer class of influenza drugs. 

Review of External Quality Assessment Programme (EQAP) panels 

EQAP was initiated in 2007 to monitor the quality of GISRS, NICs, other national influenza reference laboratories’ capacity for influenza diagnosis and detection. 

An optional antiviral phenotypic NAI panel was introduced in 2013, and genotypic baloxavir susceptibility was introduced in 2020. 

Results for the 2024 Global EQAP panel were reported during the 14th WHO-AVWG meeting. 

Of the 194 participating laboratories, 26.3% participated in NAI susceptibility testing. 

Results and subsequent discussion from this year’s panel were used by members of WHO-AVWG to assess the training needs of NICs. 

Way forward 

The 2020–2023 Annual Global Update on the Susceptibility of Influenza Viruses (Global AVS) manuscript was published{11} and drafting of a 2023–2025 publication is underway. The next WHO-AVWG meeting will be held in June 2026.

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{1} World Health Organization. Influenza Transmission Zones. 2026. https://cdn.who.int/media/docs/ default-source/influenza/influenzaupdates/2025_09_24_influenza-transmission-zones. pdf?sfvrsn=22361408_3&download=true. 

{2} Takashita E, Shimizu K, Usuku S, Senda R, Okubo I, Morita H, et al. An outbreak of influenza A(H1N1) pdm09 antigenic variants exhibiting cross-resistance to oseltamivir and peramivir in an elementary school in Japan, September 2024. Euro Surveill. 2024;29(50).

{3} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by neuraminidase inhibitors (NAIs). 2025. https://cdn.who.int/media/docs/default-source/ influenza/laboratory---network/quality-assurance/human-nai-marker-table_ for-publication_final_20240918.pdf. 

{4} World Health Organization. Summary of neuraminidase (NA) amino acid substitutions assessed for their effects on inhibition by NA inhibitors (NAIs) among avian influenza viruses of Group 1 (N1, N4, N5, N8 subtypes) and Group 2 (N2, N3, N6, N7, N9 subtypes) NAs. 2025. https://cdn.who.int/media/ docs/default-source/influenza/avwg/avian-nai-marker-whotable__10-10-2025.pdf?sfvrsn=bc0d1e9a_10 

{5} World Health Organization. Summary of polymerase acidic protein (PA) amino acid substitutions assessed for their effects on PA inhibitor (PAI) baloxavir susceptibility. 2025. https://cdn.who.int/media/docs/default-source/influenza/ laboratory---network/quality-assurance/antiviral-susceptibility-influenza/ pa-marker-who-table_28-11-2025_updated.pdf?sfvrsn=5307d6fe_4. 

{6} International Reagent Resource. 2026. https://www. internationalreagentresource.org/. 

{7} Patel MC, Flanigan D, Feng C, Chesnokov A, Nguyen HT, Elal AA, et al. An optimized cell-based assay to assess influenza virus replication by measuring neuraminidase activity and its applications for virological surveillance. Antiviral Res. 2022;208:105457. 

{8} World Health Organization. Baloxavir Susceptibility Assessment using Influenza Replication Inhibition Neuraminidase-based Assay (IRINA). https:// cdn.who.int/media/docs/default-source/influenza/avwg/cdc-phenotypic-lp492rev01d---baloxavir-susceptibility-assessment-using-irina.pdf? 

{9} Patel MC, Nguyen HT, Mishin VP, Pascua PNQ, Champion C, Lopez-Esteva M, et al. Antiviral susceptibility monitoring: testing algorithm, methods, and f indings for influenza season, 2023-2024. Antiviral Res. 2025;244:106299. 

{10} World Health Organization. Clinical practice guidelines for influenza 2024. https://www.who.int/publications/i/item/9789240097759.

{11} Hussain S, Meijer A, Govorkova EA, Dapat C, Gubareva LV, Barr I, et al. Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res. 2025:106217.

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Source: 

Link: https://iris.who.int/server/api/core/bitstreams/1ea408da-cd90-438b-b80c-b00aaf4e7315/content

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