ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2018
Oseltamivir-zanamivir combination therapy suppresses drug-resistant H1N1 influenza A viruses in the hollow fiber infection model (HFIM) system.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- A novel hollow-fiber infection model (HFIM) for antiviral PK/PD studies of CMV infection.Antimicrobial agents and chemotherapy · 2026Article
- Predictive modeling & mechanistic validation of synergistic pimodivir combinations for anti-influenza therapy via PB2cap affinity boost.NPJ digital medicine · 2025Article
- Establishment and validation of downsized hollow-fibre infection model and pharmacokinetics/pharmacodynamics analysis of VAN on Enterococcus faecium.The Journal of antimicrobial chemotherapy · 2025Article
- Inhaled Dry Powder of Antiviral Agents: A Promising Approach to Treating Respiratory Viral Pathogens.Viruses · 2025Review
- DynamicAntibiotics (Basel, Switzerland) · 2024Review
- Insights into the Structure, Metabolism, Biological Functions and Molecular Mechanisms of Sialic Acid: A Review.Foods (Basel, Switzerland) · 2023Review
- Arbidol: The current demand, strategies, and antiviral mechanisms.Immunity, inflammation and disease · 2023Review
- Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy.Microorganisms · 2023Review
- Applications of the hollow-fibre infection model (HFIM) in viral infection studies.The Journal of antimicrobial chemotherapy · 2022Review
- Assessment of influenza A (H1N1, H3N2) oseltamivir resistance during 2017-2019 in Iran.Iranian journal of microbiology · 2022Article
- Comprehensive review on molnupiravir in COVID-19: a novel promising antiviral to combat the pandemic.Future microbiology · 2022Review
- Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022Article
- Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease.Journal of biomolecular structure & dynamics · 2021Article
- Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance.Viruses · 2021Review
- ImprovedFrontiers in microbiology · 2021Article
- Article
- In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses.Viruses · 2020Article
- Early combination treatment with baloxavir and peramivir for hospitalized adults with influenza A in Yokohama, Japan.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Observational
- Influenza and antiviral resistance: an overview.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Review
- Sialic Acid-Siglec Axis as Molecular Checkpoints Targeting of Immune System: Smart Players in Pathology and Conventional Therapy.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Drug-resistant influenza is a significant threat to global public health. Until new antiviral agents with novel mechanisms of action become available, there is a pressing need for alternative treatment strategies with available influenza antivirals. Our aims were to evaluate the antiviral activity of two neuraminidase inhibitors (oseltamivir and zanamivir) as combination therapy against H1N1 influenza A viruses, as these agents bind to the neuraminidase active site differently: oseltamivir requires a conformational change for binding whereas zanamivir does not. We performed pharmacodynamic studies in the hollow fiber infection model (HFIM) system with oseltamivir (75mg Q12h, t1/2: 8h) and zanamivir (600mg Q12h, t1/2: 2.5h), given as mono- or combination therapy, against viruses with varying susceptibilities to oseltamivir and zanamivir. Each antiviral suppressed the replication of influenza strains which were resistant to the other neuraminidase inhibitor, showing each drug does not engender cross-resistance to the other compound. Oseltamivir/zanamivir combination therapy was as effective at suppressing oseltamivir- and zanamivir-resistant influenza viruses and the combination regimen inhibited viral replication at a level that was similar to the most effective monotherapy arm. However, combination therapy offered a clear benefit by preventing the emergence and spread of drug-resistant viruses. These findings demonstrate that combination therapy with two agents that target the same viral protein through distinctly different binding interactions is a feasible strategy to combat resistance emergence. This is a novel finding that may be applicable to other viral and non-viral diseases for which different classes of agents do not exist.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.