RESUMEN
For the treatment of seasonal flu and possible pandemic infections the development of new anti-influenza drugs that have good bioavailability against a broad spectrum of influenza viruses including the resistant strains is needed. In this review, we summarize previous methods for the structural modification of zanamivir, a potent neuraminidase inhibitor that has rare drug resistance, in order to develop effective anti-influenza drugs. We also report recent research into the design of multivalent zanamivir drugs and bifunctional zanamivir conjugates, some of which have shown better efficacy in animal experiments. As a step towards developing improved antivirals, conjugating anti-influenza drugs with anti-inflammatory agents can improve oral bioavailability and also exert synergistic effect in influenza therapy.
Asunto(s)
Antivirales/química , Diseño de Fármacos , Gripe Humana/tratamiento farmacológico , Neuraminidasa/antagonistas & inhibidores , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Orthomyxoviridae/enzimología , Zanamivir/análogos & derivados , Animales , Antivirales/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Gripe Humana/enzimología , Gripe Humana/virología , Terapia Molecular Dirigida , Neuraminidasa/química , Neuraminidasa/metabolismo , Orthomyxoviridae/efectos de los fármacos , Orthomyxoviridae/fisiología , Infecciones por Orthomyxoviridae/enzimología , Infecciones por Orthomyxoviridae/virología , Zanamivir/farmacologíaRESUMEN
The wizard of OS (resistance): the binding difference of neuraminidase inhibitors (zanamivir versus oseltamivir (OS)) was used to establish an assay to identify the influenza subtypes that are resistant to OS but still sensitive to zanamivir. This assay used a zanamivir-biotin conjugate to determine the OS susceptibility of a wide range of influenza viruses and over 200 clinical isolates.
