Neuraminidase Inhibitors in the Treatment of Influenza A and B - Overview and Case Reports

Wutzler, Peter; Vogel, G

doi:10.1007/s150100070016

Cited by 8 publications

(5 citation statements)

References 21 publications

(20 reference statements)

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“…Furthermore, a number of drugs have already been introduced into therapy, which were discovered by this strategy, or where rational design has played a key role in the discovery process, for example, the angiotensin‐converting‐enzyme (ACE) inhibitor captopril ( 1 ),147 the carboanhydrase inhibitor dorzolamide ( 2 ),77 the HIV‐protease inhibitors saquinavir ( 3 ), indinavir, ritonavir, and nelfinavir,148 and the sialidase inhibitors zanamivir ( 4 ) and oseltamivir (Scheme ) 149…”

Section: Introductionmentioning

confidence: 99%

Approaches to the Description and Prediction of the Binding Affinity of Small-Molecule Ligands to Macromolecular Receptors

Gohlke

Klebe

2002

Angew. Chem. Int. Ed.

753

674

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The influence of a xenobiotic compound on an organism is usually summarized by the expression biological activity. If a controlled, therapeutically relevant, and regulatory action is observed the compound has potential as a drug, otherwise its toxicity on the biological system is of interest. However, what do we understand by the biological activity? In principle, the overall effect on an organism has to be considered. However, because of the complexity of the interrelated processes involved, as a simplification primarily the "main action" on the organism is taken into consideration. On the molecular level, biological activity corresponds to the binding of a (low-molecular weight) compound to a macromolecular receptor, usually a protein. Enzymatic reactions or signal-transduction cascades are thereby influenced with respect to their function for the organism. We regard this binding as a process under equilibrium conditions; thus, binding can be described as an association or dissociation process. Accordingly, biological activity is expressed as the affinity of both partners for each other, as a thermodynamic equilibrium quantity. How well do we understand these terms and how well are they theoretically predictable today? The holy grail of rational drug design is the prediction of the biological activity of a compound. The processes involving ligand binding are extremely complicated, both ligand and protein are flexible molecules, and the energy inventory between the bound and unbound states must be considered in aqueous solution. How sophisticated and reliable are our experimental approaches to obtaining the necessary insight? The present review summarizes our current understanding of the binding affinity of a small-molecule ligand to a protein. Both theoretical and empirical approaches for predicting binding affinity, starting from the three-dimensional structure of a protein-ligand complex, will be described and compared. Experimental methods, primarily microcalorimetry, will be discussed. As a perspective, our own knowledge-based approach towards affinity prediction and experimental data on factorizing binding contributions to protein-ligand binding will be presented.

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Section: Introductionmentioning

confidence: 99%

Approaches to the Description and Prediction of the Binding Affinity of Small-Molecule Ligands to Macromolecular Receptors

Gohlke

Klebe

2002

Angew. Chem. Int. Ed.

753

674

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“…On the next day the patient discontinued zanamivir inhalation because of his good condition. Fourteen days later he felt complete recovered [66,7].…”

Section: Neuraminidase Inhibitors In Clinical Usementioning

confidence: 99%

Neuraminidase inhibitors in the management of influenza - experience of an outpatient practice

Vogel

2002

Medical Microbiology and Immunology

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The neuraminidase inhibitors signifies a breakthrough in the treatment of influenza. We compared the outcomes of influenza in 56 patients treated with zanamivir or oseltamivir to a group of 52 influenza patients from the time before these drugs were available. The duration of illness was reduced by 45%, the severity of symptoms by 40% and the administration of antibiotics by 32%. The data from this small group of patients of our ambulatory practice correspond to the results of large randomized placebo-controlled double-blind studies on zanamivir and oseltamivir. Our clinical observations and painful experiences have taught us to take every case of suspected influenza seriously. Since considerable influenza-related complications are common even in otherwise healthy individuals, patients should immediately consult their doctor when an illness with sudden onset of fever and cough or another respiratory symptom occur.

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“…When influenza outbreaks occur in these facilities, attack rates can range from 10% to 70%; 2,3 with hospitalization occurring in more than half of ill residents, and death resulting in 30% of cases 4–6 . Although more severe disease is associated with influenza A outbreaks, influenza B has also been associated with considerable morbidity and mortality, despite the availability of annual influenza vaccines for several decades 7 …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] Although more severe disease is associated with influenza A outbreaks, influenza B has also been associated with considerable morbidity and mortality, despite the availability of annual influenza vaccines for several decades. 7 Neuraminidase inhibitors (NI), such as oseltamivir and zanamvir are useful in the treatment and prophylaxis of influenza virus infections. A double blinded randomized control trial of highly vaccinated long-term care residents verified that oseltamivir pre-exposure prophylaxis led to a 92% reduction in the incidence of laboratory-confirmed influenza (P < 0AE01).…”

Section: Introductionmentioning

confidence: 99%

The use of oseltamivir during an influenza B outbreak in a chronic care hospital

Seale

Weston

Dwyer

et al. 2009

Influenza Resp Viruses

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Background Residents of nursing homes and long‐term care facilities are at a higher risk of outbreaks of influenza and of serious complications of influenza than those in the community. In late July 2005, a 90‐bed chronic care psycho‐geriatric hospital in Sydney, Australia, reported cases of influenza‐like illness (ILI) occurring amongst its residents. Methods An investigation to confirm the outbreak, and its cause, was undertaken. Influenza vaccination levels amongst residents, and the effects of antiviral drugs used for prevention and treatment, were assessed. Oseltamivir was only given to the residents, in the form of both treatment and prophylaxis. Results A total of 22 out of 89 residents met the clinical case definition of ILI with onset on or after 27 July 2005. This represents an attack rate of 25%. Oseltamivir was commenced on day 9 of the outbreak. Influenza B was identified in six residents as the causative agent of the outbreak. No deaths or acute hospitalization were recorded for this outbreak and there were no further reported cases after the introduction of oseltamivir. Vaccine effectiveness was 75% and the strain of influenza B isolated was well matched to that year’s vaccine. Conclusions There are few data on the use of oseltamivir in influenza B outbreaks. Early antiviral intervention appeared to curtail this outbreak of influenza B in a chronic care facility. We found high vaccine effectiveness in this frail, institutionalized population, highlighting the importance of influenza vaccination for residents of chronic care facilities.

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Neuraminidase Inhibitors in the Treatment of Influenza A and B - Overview and Case Reports

Cited by 8 publications

References 21 publications

Approaches to the Description and Prediction of the Binding Affinity of Small-Molecule Ligands to Macromolecular Receptors

Approaches to the Description and Prediction of the Binding Affinity of Small-Molecule Ligands to Macromolecular Receptors

Neuraminidase inhibitors in the management of influenza - experience of an outpatient practice

The use of oseltamivir during an influenza B outbreak in a chronic care hospital

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