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

Evaluation of potential influenza virus inhibitors may utilize multiple ste ps. First would be to determine if the viral target (e.g. influenza virus n euraminidase) being focused upon will be inhibited in the appropriate assay . Standard in vitro antiviral assays, used next in antiviral evaluations, m ay utilize inhibition of viral plaques, viral cytopathic effect (CPE), and viral hemagglutinin or other protein, with inhibition of viral yield used i n follow-up evaluations. The CPE can be determined visually and by dye upta ke, Animal models used for study of potential influenza virus inhibitors in clude the ferret, the laboratory mouse, and the chicken, with a variety of parameters used to indicate the severity of the infection and its inhibitio n by therapy. Multiple parameters are recommended in any in vivo antiviral evaluation. The ferret and the mouse infection models have been useful in s tudying the development of drug resistance and the relative virulence of dr ug-resistant viruses. The influenza mouse model has also been of value for the evaluation of immunomodulating effects of test compounds and for the st udy of the utility of antiviral drugs for use against influenza virus infec tions in the immunocompromised host. In considering the use of any animal m odel, species differences in drug pharmacology and metabolism must be taken into account. This review has described the systems which have been used m ost frequently by antiviral investigators, using, as examples, recent studi es with the clinically approved influenza virus neuraminidase inhibitors os eltamivir and zanamivir. (C) 2000 Elsevier Science B.V. All rights reserved .