Antivirals: Targets and use

Ison, Michael G.; Hay, Alan J.

doi:10.1002/9781118636817.ch25

Cited by 4 publications

(6 citation statements)

References 128 publications

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“…We examined the effect of seven NA amino acid substitutions (E119A, D198E, D198Y, I222T, H274Y, N294S, and R371K) on NAI susceptibility, genetic stability, NA biochemical properties, and viral replication efficiency in vitro. All seven NA substitutions have been isolated from patients undergoing antiviral treatment or identified during surveillance studies and are associated with reduced inhibition by NAIs (17,(27)(28)(29). Out of these seven NA substitutions, three (D198E, I222T, and N294S) were selected from the list of substitutions associated with reduced NAI inhibition of influenza B viruses following the recommendations of the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) (30)(31)(32).…”

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confidence: 99%

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Burnham

Baranovich

Marathe

et al. 2014

Antimicrob Agents Chemother

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Influenza B viruses cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major cause of influenza-associated pediatric mortality. Neuraminidase (NA) inhibitors (NAIs) are the only available therapy for patients infected with influenza B viruses, and the potential emergence of NAI-resistant viruses is a public health concern. The NA substitutions located within the enzyme active site could not only reduce NAI susceptibility of influenza B virus but also affect virus fitness. In this study, we investigated the effect of single NA substitutions on the fitness of influenza B/Yamanashi/166/1998 viruses (Yamagata lineage). We generated recombinant viruses containing either wild-type (WT) NA or NA with a substitution in the catalytic (R371K) or framework (E119A, D198E, D198Y, I222T, H274Y, and N294S) residues. We assessed NAI susceptibility, NA biochemical properties, NA protein expression, and virus replication in vitro and in differentiated normal human bronchial epithelial (NHBE) cells. Our results showed that four NA substitutions (D198E, I222T, H274Y, and N294S) conferred reduced inhibition by oseltamivir and three (E119A, D198Y, and R371K) conferred highly reduced inhibition by oseltamivir, zanamivir, and peramivir. All NA substitutions, except for D198Y and R371K, were genetically stable after seven passages in MDCK cells. Cell surface NA protein expression was significantly increased by H274Y and N294S substitutions. Viruses with the E119A, I222T, H274Y, or N294S substitution were not attenuated in replication efficiency in vitro or in NHBE cells. Overall, viruses with the E119A or H274Y NA substitution possess fitness comparable to NAI-susceptible virus, and the acquisition of these substitutions by influenza B viruses should be closely monitored.

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confidence: 99%

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Burnham

Baranovich

Marathe

et al. 2014

Antimicrob Agents Chemother

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“…Since the widespread global resistance to the adamantane M2 ion channel inhibitors in the mid-2000s ( 13 , 14 ), the neuraminidase inhibitors (NAIs) have been the best drugs available to treat severe influenza infections ( 15 ). Zanamivir (ZA) and oseltamivir have been globally approved since 1999, whereas peramivir and laninamivir have been approved in Japan and a few other countries since 2010 ( 13 , 16 ).…”

Section: Neuraminidase Inhibitors and Resistancementioning

confidence: 99%

“…OC and all other NAIs act by competitive binding to the extracellular enzymatic site of the neuraminidase (NA) protein. Thereby, the NA binding and the catalytic destruction of its sialic acid targets is inhibited and the release of newly formed virions from infected cells and viral spread through respiratory secretions is reduced ( 16 ). NAI binding to the enzymatic target differs slightly between the structurally different neuraminidase (NA) proteins ( 20 ), which are phylogenetically grouped to Group 1 (including subtypes N1, N4, N5, N8) and Group 2 (including subtypes N2, N3, N6, N7 and N9) ( 1 , 21 ).…”

Section: Neuraminidase Inhibitors and Resistancementioning

confidence: 99%

Risk of resistant avian influenza A virus in wild waterfowl as a result of environmental release of oseltamivir

Gillman

2016

Infection Ecology & Epidemiology

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Oseltamivir is the best available anti-influenza drug and has therefore been stockpiled worldwide in large quantities as part of influenza pandemic preparedness planning. The active metabolite oseltamivir carboxylate (OC) is stable and is not removed by conventional sewage treatment. Active OC has been detected in river water at concentrations up to 0.86 µg/L. Although the natural reservoir hosts of influenza A virus (IAV) are wild waterfowl that reside in aquatic environments, the ecologic risks associated with environmental OC release and its potential to generate resistant viral variants among wild birds has largely been unknown. However, in recent years a number of in vivo mallard (Anas platyrhynchos) studies have been conducted regarding the potential of avian IAVs to become resistant to OC in natural reservoir birds if these are drug exposed. Development of resistance to OC was observed both in Group 1 (N1) and Group 2 (N2, N9) neuraminidase subtypes, when infected ducks were exposed to OC at concentrations between 0.95 and 12 µg/L in their water. All resistant variants maintained replication and transmission between ducks during drug exposure. In an A(H1N1)/H274Y virus, the OC resistance mutation persisted without selective drug pressure, demonstrating the potential of an IAV with a permissive genetic background to acquire and maintain OC resistance, potentially allowing circulation of the resistant variant among wild birds. The experimental studies have improved the appreciation of the risks associated with the environmental release of OC related to resistance development of avian IAVs among wild birds. Combined with knowledge of efficient methods for improved sewage treatment, the observations warrant implementation of novel efficient wastewater treatment methods, rational use of anti-influenza drugs, and improved surveillance of IAV resistance in wild birds.

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“…Depending on the type of test, the results are obtained within several hours (9,10) . This is of key importance for the initiation of treatment, which should be implemented 36-48 hours after the onset of first symptoms and involve the use of new generation anti-influenza drugs (5,8,(11)(12)(13)(14)(15) . Influenza is not a pathognomonic disease.…”

mentioning

confidence: 99%

“…small children, chronically ill patients, patients on immunosuppressive therapy, the elderly and high-risk patients, who may experience severe illness and complications compared to potentially healthy individuals (high risk of complications) (1,4,8,12) . For this reason, it is important to rapidly identify the aetiological factor to decide on further management, considering the possible use of new generation anti-influenza drugs -neuraminidase inhibitors (4,7,8,11,13) . Laboratory diagnosis involves: • confirmation of influenza virus antigen in the material collected from the patient; • serological confirmation of influenza virus infection based on increased serum antibody levels.…”

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confidence: 99%

Laboratory diagnosis of influenza

Byambasuren¹,

Brydak

2018

PEDIATR MED RODZ

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Influenza has always been and still is the cause of considerable morbidity and, consequently, frequent multiorgan complications, often irreversible and even fatal. It is an acute infectious disease caused by type A, B and C viruses, members of the family Orthomyxoviridae. Infections caused by the influenza virus are reported in every epidemic season. Influenza infections should be considered not only in the aspect of health, but also in the quantifiable, measurable economic aspect. For many years, influenza has been one of the basic priorities of public health. Virological and epidemiological surveillance of influenza, which is implemented in each epidemiological season, is one of the key elements of public health. Virological surveillance involves laboratory confirmation of infection, while epidemiological surveillance involves monitoring of actual and suspected cases of influenza. Laboratory diagnosis is performed to confirm influenza virus antigen in the material collected from the patient, isolate the virus and confirm viral infection based on increased serum antibody levels. Isolating influenza viruses that circulate in a given epidemiological season is necessary to prepare a vaccine against influenza. An early and correct virological diagnosis of respiratory infection, with particular reference to influenza, is currently of great importance in terms of both medical and economic aspects. The paper discusses influenza diagnostic methods currently used in Poland to help physicians in deciding whether laboratory confirmation of diagnosis is justified in the aspect of possible treatment to avoid influenza-induced multiple organ complications.

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Antivirals: Targets and use

Cited by 4 publications

References 128 publications

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Risk of resistant avian influenza A virus in wild waterfowl as a result of environmental release of oseltamivir

Laboratory diagnosis of influenza

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