The Value of Neuraminidase Inhibitors for the Prevention and Treatment of Seasonal Influenza: A Systematic Review of Systematic Reviews

Michiels, Bart; Puyenbroeck, Karolien Van; Verhoeven, Véronique; Vermeire, Etienne; Coenen, Samuel

doi:10.1371/journal.pone.0060348

Cited by 108 publications

(69 citation statements)

References 89 publications

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“…This finding confirms previous estimates and is comparable with observed effects of oseltamivir 2 4. No treatment effect was seen on pneumonia.…”

Section: Commentarysupporting

confidence: 92%

“…Previous systematic reviews (SRs) of zanamivir may have been affected by publication bias and missing data, and clinical recommendations based on such studies should be considered inadequate 1 2. To deal with these shortcomings, this SR and meta-analysis (an update of a Cochrane Review)3 reanalysed the prophylactic and treatment effects of zanamivir on those suffering from influenza, based on the full clinical study reports of all relevant trials provided by the manufacturer and on regulatory comments.…”

Section: Contextmentioning

confidence: 99%

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Zanamivir for influenza in adults and children shows limited benefit for treatment of symptomatic influenza and no effect on relevant complications

Michiels

2014

Evid Based Med

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“…This finding confirms previous estimates and is comparable with observed effects of oseltamivir 2 4. No treatment effect was seen on pneumonia.…”

Section: Commentarysupporting

confidence: 92%

Section: Contextmentioning

confidence: 99%

Zanamivir for influenza in adults and children shows limited benefit for treatment of symptomatic influenza and no effect on relevant complications

Michiels

2014

Evid Based Med

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“…Meta-analysis has been used to identify significance and draw conclusions from the numerous and disparate reports of oseltamivir efficacy (Ebell et al, 2013; Jefferson et al, 2012; Michiels et al, 2013; Wang et al, 2012). Unfortunately, these meta-analyses have not delineated NAI treatment for influenza B, but have suggested that oseltamivir is marginally effective in reducing the duration of illness for all influenza infections.…”

Section: Nais For the Control Of Influenza Bmentioning

confidence: 99%

Neuraminidase inhibitors for influenza B virus infection: Efficacy and resistance

2013

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Many aspects of the biology and epidemiology of influenza B viruses are far less studied than for influenza A viruses, and one of these aspects is effectiveness and resistance to the clinically available antiviral drugs, the neuraminidase (NA) inhibitors (NAIs). Acute respiratory infections are one of the leading causes of death in children and adults, and influenza is among the few respiratory infections that can be prevented and treated by vaccination and antiviral treatment. Recent data has suggested that influenza B virus infections are of specific concern to pediatric patients because of the increased risk of severe disease. Treatment of influenza B is a challenging task for the following reasons: NAIs (e.g., oseltamivir and zanamivir) are the only FDA-approved class of antivirals available for treatment;the data suggest that oseltamivir is less effective than zanamivir in pediatric patients;zanamivir is not prescribed to patients younger than 7;influenza B viruses are less susceptible than influenza A viruses to NAIs in vitro;although the level of resistance to NAIs is low, the number of different molecular markers of resistance is higher than for influenza A viruses, and they are not well defined;the relationship between levels of NAI phenotypic resistance and known molecular markers, frequency of emergence, transmissibility, and fitness of NAI-resistant variants are not well established. This review presents current knowledge of the effectiveness of NAIs for influenza B virus and antiviral resistance in clinical, surveillance, and experimental studies.

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“…The current standard of care is treatment using the neuraminidase inhibitors oseltamivir and zanamivir. It is recommended that treatment begin as early as possible after the onset of illness, ideally within 48 h. The benefit of these agents has recently received considerable scrutiny, with several observational studies reporting reduced mortality in treated individuals during the recent H1N1pdm09 pandemic (17-19) whereas other reviews have questioned this observation (20,21). In addition to the limited treatment window, another concern for this class of antivirals is the possibility of neuraminidase inhibitor resistance, as occurred during the 2008 to 2009 season when oseltamivir-resistant H1N1 was prevalent (22,23).…”

mentioning

confidence: 99%

Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit

Byrn

Jones

Bennett

et al. 2015

Antimicrob Agents Chemother

169

189

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h VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m 7 GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a K D (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC 50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC 50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection. Influenza is a potentially deadly infectious disease that has imposed a substantial burden in terms of morbidity and mortality on human populations (1). Recent statistics suggest that, each year in the United States, 5% to 20% of the population becomes infected with influenza virus, with more than 200,000 hospitalizations for respiratory and heart-related complications and an annual mortality rate ranging from ϳ3,000 to 49,000 deaths (2, 3).Vaccination has become the mainstay of efforts to minimize the impact of seasonal influenza (4, 5), and while generally effective in healthy adults, it is often less effective in elderly individuals, and there have been recent examples where predictions of which viral strains to include have been inadequate (6, 7). Further, the 2009 H1N1 pandemic demonstrated that the logistics required to rapidly isolate and identify the correct strain and to produce enough vaccine worldwide was quite challenging (8-10). The continued incidence of human infection by avian influenza virus strains, namely, either the highly pathogenic H5N1 or H7N7 subtypes or the recently emerging low pathogenic H7N9 and H10N9 strains, represents an additional challenge for vaccine development strategies (11-15) Antiviral agents may be used for the prophylaxis of influenza virus infection (mainly in high-risk settings) or in a treatment modality for the reduction of illness duration. They may also provide an option for rapid deployment during a pandemic situati...

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The Value of Neuraminidase Inhibitors for the Prevention and Treatment of Seasonal Influenza: A Systematic Review of Systematic Reviews

Cited by 108 publications

References 89 publications

Zanamivir for influenza in adults and children shows limited benefit for treatment of symptomatic influenza and no effect on relevant complications

Zanamivir for influenza in adults and children shows limited benefit for treatment of symptomatic influenza and no effect on relevant complications

Neuraminidase inhibitors for influenza B virus infection: Efficacy and resistance

Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit

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