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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#Treatment of #CCHF with supportive care, #favipiravir, and avatrombopag

 

Abstract

We report a severe Crimean-Congo Hemorrhagic Fever case treated with favipiravir and avatrombopag in a high-level isolation unit. This multimodal approach was associated with rapid platelet recovery, reduced transfusion requirements, and viral clearance. Combining targeted antivirals with thrombopoietin receptor agonists represents a promising strategy for managing severe CCHF coagulopathy.

Source: 

Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag415/8765585?redirectedFrom=fulltext

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#Maraviroc Inhibits #SARS-CoV-2 Through Variant-Dependent Effects on Viral Entry and #Mpro Activity Using Single-Round Infectious Particle and Virus-like Particle Models

 

Abstract

Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC50 values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell–cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC50 = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/911

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#Lassa fever and Argentine hemorrhagic fever #treatment in guinea pigs using broad-spectrum cap-dependent #endonuclease #inhibitors

 

ABSTRACT

The class Bunyaviricetes encompasses several highly pathogenic viruses that cause lethal hemorrhagic fevers. Due to their limited prevention and treatment options and high pathogenicity, these viruses require handling in biosafety level-4 facilities. Within the bunyaviruses, arenaviruses are particularly notable for their pathogenicity and ability to cause severe hemorrhagic disease in humans. The cap-dependent endonuclease (CEN) is a unique and crucial enzyme involved in the replication cycle of these viruses. As humans do not possess a similar enzyme, CEN represents an ideal target for antiviral drug development with reduced risk of side effects. Recently, we identified a promising CEN inhibitor (CENi) demonstrating potent inhibition of virus replication. In this manuscript, we demonstrate the successful therapeutic efficacy of CENis against Lassa fever and Argentine hemorrhagic fever virus infections in guinea pig models of lethal hemorrhagic fever. In addition, we identified several CENis with antiviral activity against other highly pathogenic arenaviruses. These findings further support the potential of CENis as therapeutic agents for arenavirus infections that cause severe and often lethal hemorrhagic fever. Collectively, our results suggest that CENis are promising candidates for pan-arenavirus therapy and may also have broader utility against other CEN-containing viruses for which no approved antiviral treatments currently exist.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00880-26

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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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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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