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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An imported case of #Bundibugyo virus #infection, #France, June 2026

 

Abstract

In June 2026, an intensive care physician deployed in the Democratic Republic of the Congo and previously vaccinated against Ebola virus developed fatigue, nausea and headaches while returning to France. Bundibugyo virus was identified with RT-PCR. The patient was treated with remdesivir and recovered fully. Contact tracing identified five low-risk contacts and no secondary cases. Stringent infection prevention and control measures and multidisciplinary collaboration are important when managing suspected or confirmed Ebola disease cases, even with low viral loads.

Source: 

Link: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2026.31.31.2600627?emailalert=true#abstract_content

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The relationship between #plasma #favipiravir concentrations and #clinical #outcomes in #COVID19

 

Abstract

Background

Favipiravir has shown efficacy against SARS-CoV-2 in patients <60 years old, but data linking plasma concentrations to clinical outcomes are limited. This study investigated whether favipiravir plasma concentrations influence clinical efficacy and outcomes in patients hospitalised with COVID-19. The main research question was, How can antiviral dosing strategies be optimised to improve pandemic preparedness and treatment efficacy?

Methods

Adult participants were drawn from the PIONEER trial, in which patients received oral favipiravir (1800 mg twice daily for 1 day, then 800 mg twice daily for 9 days) plus standard care. This analysis included patients with confirmed COVID-19 and ≥75% study adherence. Samples were collected between days 5 and 10 post-treatment initiation. The primary outcome was time to clinical improvement. Secondary outcomes included achievement of clinical improvement and mortality risk.

Results

Out of 140 patients (50% male; mean±sd age 59.5±14.8 years), target plasma concentrations were reached in 29 (21%). Mean time to improvement was 7.7±5.9 days in target achievers versus 9.1±7.2 days in non-achievers (p=0.26). The target was more often achieved in female (34%) than male (7%) participants (p=0.0002). Plasma concentration inversely correlated with body mass index (r= –0.4, p<0.0001), and with lower body mass index in achievers (26.0±5.1 kg·m−2 versus 30.5±6.9 kg·m−2, p=0.003). Alkaline phosphatase and alanine aminotransferase levels were also lower in achievers (p=0.004 and p=0.02, respectively).

Conclusion

Most patients did not reach target favipiravir levels. Concentrations were influenced by sex, body mass index and liver function, confirming the need for pharmacokinetically guided dosing and therapeutic monitoring to optimise antiviral efficacy in future pandemic responses.

Shareable abstract @ERSpublications

Plasma favipiravir concentrations vary with sex, BMI and liver function. Concentrations in most patients fail to reach therapeutic levels, highlighting the need for personalised, pharmacokinetically guided dosing to optimise antiviral efficacy in future pandemics. https://bit.ly/4a6PvEa

Source: 

Link: https://publications.ersnet.org/content/erjor/12/4/01560-2025

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Synergistic #antiviral effect of #Asunaprevir and #Ribavirin in combination against Murray Valley #Encephalitis Virus replication

 

Highlights

    • Renilla luciferase-based MVEV sub-genomic replicon was constructed and applied in antiviral drug evaluation.

    • Removal of Stem Loop I from 3’UTR impairs viral genome replication.

    • Asunaprevir and ribavirin exhibit synergistic antiviral activity against MVEV.

    • A single-round MVEV infectious particle platform was developed.

Abstract

Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known for causing severe neurological diseases in humans. Despite the rising number of reported infections and high mortality rate among hospitalized patients, no antiviral therapies or licensed vaccines are available. To strengthen preparedness against this reemerging virus, we establish a subgenomic replicon (SGR) platform and a complementary single-round infectious particles (SRIPs) production system, using widely circulating genotype 1 (G1) MVEV as backbone. Stem-loop I(SLI) from 3’UTR stands for the major difference among 4 MVEV genotypes and removal of SLI resulted in mild decrease of genome replication. Through screening a mini anti-flavivirus drug library, we identified that asunaprevir (ASV) and ribavirin (RBV) inhibit MVEV infection independently. Combination of ASV and RBV also showed synergistic activity against MVEV. These results underscore the value of the MVEV replicon system as a versatile tool for evaluating antiviral compounds, supporting the potential of ASV and RBV as a combinatorial therapeutic approach.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226001567?via%3Dihub

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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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#Nirmatrelvir for acute #COVID19 to prevent #longCOVID (PANORAMIC Norway): a double-blind, randomised, placebo-controlled trial

 

Summary

Background

Long-term symptoms are common after acute COVID-19, particularly fatigue, cognitive problems, and dyspnoea. Cohort studies have suggested that antiviral treatment of acute COVID-19 might prevent development of post-COVID-19 condition (also known as long COVID), but the efficacy of antivirals has yet to be verified in prospective studies. We aimed to investigate whether treatment of acute SARS-CoV-2 infection with nirmatrelvir–ritonavir would reduce the risk of long COVID.

Methods

In this double-blind, randomised, placebo-controlled trial, participants were recruited from the municipal health-care service at three sites in Norway (Bergen, Oslo, and Ålesund). Non-hospitalised adults aged 18–65 years with SARS-CoV-2 infection confirmed by PCR or lateral flow test and symptoms for 5 days or fewer were eligible for inclusion. Key exclusion criteria included pregnancy or lactation, chronic renal impairment or chronic liver dysfunction, and any person judged by the investigator to need nirmatrelvir–ritonavir treatment due to increased risk of hospitalisation or death. Participants were allocated in a 1:1 ratio to receive oral 300 mg nirmatrelvir and 100 mg ritonavir, or placebo, twice a day for 5 days using a pre-generated randomisation list without stratification or block adjustment. Participants, clinicians, and the study team were masked to treatment allocation. The primary outcome was long COVID, defined as patient-reported fatigue, dyspnoea, and/or cognitive symptoms at 3 months’ follow-up. Safety was analysed as a secondary outcome, and included adverse events, hospital admissions, and deaths. Both the primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (NCT05852873) and is now closed to new participants.

Findings

Between May 12, 2023, and June 11, 2025, we enrolled 144 participants, of whom 66 were assigned to nirmatrelvir–ritonavir and 78 to placebo. In the protocol we planned to enrol 2000 participants, but the trial was stopped prematurely by the steering committee due to insufficient recruitment. Among the 143 participants who completed follow-up, the risk of long COVID at 3 months was significantly reduced in the nirmatrelvir–ritonavir group (17 [26%] of 66) compared with the placebo group (33 [43%] of 77), corresponding to a relative risk after imputation of data for the single missing value in the placebo group of 0·60 (95% CI 0·37–0·98; p=0·039). In the nirmatrelvir–ritonavir group, five patients discontinued treatment due to adverse events. The most common adverse events in the nirmatrelvir–ritonavir group were change in taste or smell (57 [86%] of 66 in the nirmatrelvir–ritonavir group vs 14 [18%] of 78 in the placebo group) and nausea or vomiting (19 [29%] vs eight [10%]). Inversely, palpitations were more common in the placebo group (ten [13%] of 78) than in the nirmatrelvir-ritonavir group (two [3%] of 66). No severe adverse events were reported.

Interpretation

Treatment with nirmatrelvir–ritonavir for acute COVID-19 was associated with a significant reduction in the risk of long COVID at 3 months’ follow-up. The limited sample size precludes firm conclusions, and further clinical trials are warranted.

Funding

National Health Authorities’ KlinBeForsk programme, Western Norway Regional Health Authority, Helse Møre og Romsdal Hospital Trust, and The Influenza Centre, Haukeland University Hospital and University of Bergen, Bergen, Norway.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00244-6/fulltext?rss=yes

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#Ribavirin post-exposure #prophylaxis for #Andes virus #exposure: a viewpoint

 

Summary

Andes virus (ANDV) is unique among hantaviruses because person-to-person transmission is possible. This raises questions on the relevance of post-exposure prophylaxis (PEP), particularly following high-risk household, healthcare-associated, or laboratory exposures, considering its high case fatality rate. Ribavirin has demonstrated antiviral activity against hantaviruses in vitro and in animal models, although clinical evidence supporting its use for ANDV remains extremely limited. This viewpoint summarises the currently available evidence regarding ribavirin as PEP after potential ANDV exposure. We discuss the knowledge gaps that may limit the applicability of ribavirin PEP, to make informed decisions on the use of ribavirin in the setting of PEP. Potential dosing strategies are visualised by modelling and simulation, and potential dose and duration are discussed. Although the biological rationale for ribavirin PEP appears compelling, absence of controlled human studies and potential toxicity currently limit its role to highly selected exposure scenarios and use shortly after exposure.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00270-7/fulltext

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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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#Pixavir Marboxil: First Approval

 

Abstract

Pixavir marboxil (Yilikang®; 壹立康®) is an oral cap-snatching endonuclease inhibitor being developed by TaiGen Biotechnology for the treatment of influenza virus infections. Pixavir marboxil recently received approval in China for the treatment of uncomplicated influenza A and B in previously healthy adults and adolescents aged ≥ 12 years. This article summarizes the milestones in the development of pixavir marboxil leading to this first approval for uncomplicated influenza A and B infections.

Source: 

Link: https://link.springer.com/article/10.1007/s40265-026-02320-2

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Effectiveness of #baloxavir marboxil in nonhuman #primates infected with highly pathogenic avian #influenza #H7N9 virus

 

Summary

Background

Highly pathogenic avian influenza (HPAI) A(H7N9) virus poses a potential public health threat, underscoring the need for effective antiviral options for outbreak preparedness. Baloxavir marboxil (BXM) is a cap-dependent endonuclease inhibitor approved for seasonal influenza, but its in vivo efficacy against HPAI A(H7N9) virus has not been fully evaluated.

Methods

We evaluated the efficacy of BXM in cynomolgus macaques infected with a reverse genetics-generated HPAI A(H7N9) virus. Animals received either low- or high-dose BXM, single-dose oseltamivir, or vehicle at 4 or 48 h post-infection (hpi). BXM administration was designed to mimic human pharmacokinetics. Viral titres, body temperature, body weight, lung pathology, and treatment-emergent viral substitutions were analysed.

Findings

Early treatment (4 hpi) with BXM significantly reduced viral titres in nasal and tracheal swabs, lessened weight loss, and decreased pulmonary inflammation and alveolar damage compared to untreated or oseltamivir-treated animals. Virus pathogenicity was relatively mild; no animals died. Delayed treatment (48 hpi) showed limited benefit. The PA-I38T (83.8%) and PA-E23G (78.6%) substitutions associated with BXM resistance were detected in one animal, and a PA-K34R (85.4%) substitution was detected in another animal. These substitutions reduce BXM susceptibility and were detected at low titres.

Interpretation

Although the dosing regimen used in this study involved repeat dosing to achieve the plasma drug concentrations after a single dose in humans, these findings highlight the importance of early antiviral intervention and support BXM use as a potential countermeasure against HPAI A(H7N9) virus infection, as resistance-associated substitutions remained limited in the macaque model. BXM may be a valuable therapeutic option for HPAI A(H7N9) virus infections.

Funding

Supported by the Japan Agency for Medical Research and Development (JP20wm0125002, JP223fa627001) and Shionogi & Co., Ltd.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00233-1/fulltext

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A #drug #repurposing screen identifies #antiviral compounds against #Puumala #Orthohantavirus

Abstract

Hantaviruses are zoonotic negative-sense RNA viruses that cause haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), yet no approved antiviral therapies are available. To identify host-directed modulators of hantavirus infection we performed a drug repurposing screen using live Puumala virus (PUUV). We identified and validated 70 drugs with antiviral activity in A549 cells and primary human endothelial cells. Functional clustering confirmed the known infection-inhibitory effect of several groups of compounds, including inhibitors of heat shock proteins, mTOR pathway and nucleotide synthesis. Our screen also identified compounds yet unexplored as antivirals against Hantaviruses, such as certain antibiotics. Our dataset provides a systematic map of host pathways influencing PUUV infection and highlights candidate compounds and cellular processes that can modulate this process.

Source: 

Link: https://www.nature.com/articles/s41598-026-57843-1

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Epidemiological and Virological Characteristics of #H9N2 Avian #Influenza Virus in #Jiangsu Province, #China, 2024

 

Abstract

H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended.

Source: 

Link: https://www.mdpi.com/1999-4915/18/6/687

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Potent In Vitro #Antiviral Activity of 4'-Fluorouridine Against Diverse #Orthohantaviruses including #Andes Virus

 

Highlights:

    • 4′-fluorouridine exhibits broad-spectrum activity against 16 orthohantaviruses.

    • The compound inhibits hantavirus replication by targeting the viral polymerase.

    • Efficacy is maintained in human endothelial and airway epithelial cells.

Abstract

Hantaviruses are emerging pathogens responsible for severe and often fatal diseases, including hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), for which no FDA-approved antivirals currently exist. Using a Seoul virus minigenome system, we first confirmed that the ribonucleoside analog 4’-fluorouridine (EIDD-2749) effectively targets the hantavirus polymerase complex, inhibiting viral RNA transcription and replication. We subsequently evaluated its antiviral activity against a comprehensive panel of 16 hantaviruses representing both Old and New World lineages including both the Chilean and Argentinian strains of Andes virus. 4’-fluorouridine demonstrated potent, dose-dependent inhibition across all viruses tested, with EC50 values uniformly in the low- to sub-micromolar range. Collectively, these findings establish 4’-fluorouridine as a highly potent, pan-hantavirus inhibitor and a promising candidate for further preclinical development.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226001269?via%3Dihub

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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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#Human ACE2‑specific benzothiazole-based allosteric #inhibitor against pan ‑ #sarbecoviruses

 

Abstract

Emerging SARS‑CoV‑2 variants and related zoonotic sarbecoviruses rely on ACE2 for cell entry, motivating host‑directed antivirals that block spike-ACE2 interaction. Here, we characterize MB‑32, a benzothiazole small molecule that binds ACE2, selectively disrupts binding of SARS‑CoV‑2 spike receptor‑binding domain to ACE2, and preserves ACE2 enzymatic activity across species. MB‑32 potently inhibits entry of SARS‑CoV‑2 variants, SARS‑CoV‑1 and diverse bat/pangolin sarbecoviruses in ACE2‑expressing cells, while sparing vesicular stomatitis virus and authentic MERS‑CoV, indicating non‑virucidal, ACE2‑focused activity. Biochemical and biophysical analyses, supported by ACE2 mutagenesis, support a model in which MB‑32 engages a non‑catalytic surface pocket on the ACE2 N‑terminal helix to allosterically disrupt spike attachment. Intranasal MB‑32 achieves high airway concentrations, protects male ACE2‑transgenic mice and hamsters from SARS‑CoV‑2 disease, and prevents contact transmission of Omicron‑lineage viruses without detectable cardiovascular toxicity. These findings establish MB‑32 as a host‑targeted ACE2 entry inhibitor and provide a framework for small‑molecule ACE2‑directed antivirals against current and future sarbecovirus spillovers.

Source: 

Link: https://www.nature.com/articles/s41467-026-73944-x

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Identification and characterization of a #SARS-CoV-2 #Mpro G23 deletion #ensitrelvir - #resistant mutant

 

ABSTRACT

Ensitrelvir is an antiviral drug that specifically targets the conserved main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, mutations in Mpro could confer resistance to antivirals, including ensitrelvir. Thus, identifying SARS-CoV-2 drug-resistant mutants and elucidating their mechanisms of resistance are critical for guiding the selection of effective antiviral therapies. Here, we utilized a recombinant luminescent attenuated SARS-CoV-2 lacking the open reading frames (ORF) 3a and 7b proteins (Δ3a7b-Nluc WT) to safely identify ensitrelvir drug-resistant mutants (DRM-E) without the need of using virulent forms of SARS-CoV-2. We isolated a DRM-E containing a Mpro G23 deletion (G23del) with high resistance (~1,000-fold) to ensitrelvir, but not to the Mpro inhibitor nirmatrelvir or to the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir. The contribution of G23del in ensitrelvir resistance was confirmed by generating a Δ3a7b-Nluc containing G23del in Mpro (Δ3a7b-Nluc G23del). Δ3a7b-Nluc G23del exhibited resistance to ensitrelvir in both cultured cells and in K18 hACE2 transgenic mice. Binding affinity revealed that the G23del mutation altered ensitrelvir, but not nirmatrelvir, binding to Mpro. Notably, while Δ3a7b-Nluc G23del was affected in viral fitness, serial passage of Δ3a7b-Nluc G23del in the absence of ensitrelvir resulted in the emergence of substitution L50F in Mpro that restored viral fitness loss caused by G23del without altering resistance to ensitrelvir. Our results demonstrate that G23del in Mpro can confer resistance to ensitrelvir. Positively, G23del in Mpro does not render SARS-CoV-2 resistant to nirmatrelvir or remdesivir, suggesting the feasibility of treating SARS-CoV-2 infections containing G23del Mpro with other approved antivirals.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00584-26

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