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In vitro and in vivo assay systems for study of influenza virus inhibitors

Identifieur interne : 001951 ( Main/Exploration ); précédent : 001950; suivant : 001952

In vitro and in vivo assay systems for study of influenza virus inhibitors

Auteurs : Robert W. Sidwell [États-Unis] ; Donald F. Smee [États-Unis]

Source :

RBID : ISTEX:D3D663E5809BFAE4596290743862F1E678A9F78B

English descriptors

Abstract

Abstract: Evaluation of potential influenza virus inhibitors may utilize multiple steps. First would be to determine if the viral target (e.g. influenza virus neuraminidase) being focused upon will be inhibited in the appropriate assay. Standard in vitro antiviral assays, used next in antiviral evaluations, may utilize inhibition of viral plaques, viral cytopathic effect (CPE), and viral hemagglutinin or other protein, with inhibition of viral yield used in follow-up evaluations. The CPE can be determined visually and by dye uptake. Animal models used for study of potential influenza virus inhibitors include the ferret, the laboratory mouse, and the chicken, with a variety of parameters used to indicate the severity of the infection and its inhibition by therapy. Multiple parameters are recommended in any in vivo antiviral evaluation. The ferret and the mouse infection models have been useful in studying the development of drug resistance and the relative virulence of drug-resistant viruses. The influenza mouse model has also been of value for the evaluation of immunomodulating effects of test compounds and for the study of the utility of antiviral drugs for use against influenza virus infections in the immunocompromised host. In considering the use of any animal model, species differences in drug pharmacology and metabolism must be taken into account. This review has described the systems which have been used most frequently by antiviral investigators, using, as examples, recent studies with the clinically approved influenza virus neuraminidase inhibitors oseltamivir and zanamivir.

Url:
DOI: 10.1016/S0166-3542(00)00125-X


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Academic press</term>
<term>Agents chemother</term>
<term>Amantadine</term>
<term>Animal model</term>
<term>Animal models</term>
<term>Anti6iral</term>
<term>Antimicrob</term>
<term>Antiviral</term>
<term>Antiviral activity</term>
<term>Antiviral assays</term>
<term>Antiviral chem</term>
<term>Antiviral compounds</term>
<term>Antiviral drugs</term>
<term>Antiviral effect</term>
<term>Antiviral investigators</term>
<term>Appropriate assay</term>
<term>Arterial oxygen saturation</term>
<term>Assay</term>
<term>Avian virus</term>
<term>Cell culture</term>
<term>Challenge dose</term>
<term>Chemother</term>
<term>Chick embryo</term>
<term>Chicken model</term>
<term>Clinical studies</term>
<term>Consolidation score</term>
<term>Drinking water</term>
<term>Drug pharmacology</term>
<term>Effective concentration</term>
<term>Elsevier science</term>
<term>Epithelial cells</term>
<term>Extracellular virus yields</term>
<term>Febrile response</term>
<term>Hayden</term>
<term>Huffman</term>
<term>Identical virus pool</term>
<term>Immune</term>
<term>Immune response</term>
<term>Immune system</term>
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<term>Mist study group</term>
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<term>Multiple parameters</term>
<term>Mutant virus</term>
<term>Mutation</term>
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<term>Oral treatment</term>
<term>Oseltamivir</term>
<term>Oseltamivir carboxylate</term>
<term>Parent compound</term>
<term>Parental virus</term>
<term>Plaque formation</term>
<term>Potential virus inhibitors</term>
<term>Pulse oximeter</term>
<term>Rate doses</term>
<term>Relative virulence</term>
<term>Replication</term>
<term>Respective drugs</term>
<term>Respiratory tract</term>
<term>Ribavirin</term>
<term>Rimantadine</term>
<term>Sao2</term>
<term>Sao2 decline</term>
<term>Sao2 values</term>
<term>Selective index</term>
<term>Serial passage</term>
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<term>Single passage</term>
<term>Smee</term>
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<div type="abstract" xml:lang="en">Abstract: Evaluation of potential influenza virus inhibitors may utilize multiple steps. First would be to determine if the viral target (e.g. influenza virus neuraminidase) being focused upon will be inhibited in the appropriate assay. Standard in vitro antiviral assays, used next in antiviral evaluations, may utilize inhibition of viral plaques, viral cytopathic effect (CPE), and viral hemagglutinin or other protein, with inhibition of viral yield used in follow-up evaluations. The CPE can be determined visually and by dye uptake. Animal models used for study of potential influenza virus inhibitors include the ferret, the laboratory mouse, and the chicken, with a variety of parameters used to indicate the severity of the infection and its inhibition by therapy. Multiple parameters are recommended in any in vivo antiviral evaluation. The ferret and the mouse infection models have been useful in studying the development of drug resistance and the relative virulence of drug-resistant viruses. The influenza mouse model has also been of value for the evaluation of immunomodulating effects of test compounds and for the study of the utility of antiviral drugs for use against influenza virus infections in the immunocompromised host. In considering the use of any animal model, species differences in drug pharmacology and metabolism must be taken into account. This review has described the systems which have been used most frequently by antiviral investigators, using, as examples, recent studies with the clinically approved influenza virus neuraminidase inhibitors oseltamivir and zanamivir.</div>
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