Sialidase as a target for inhibitors of influenza virus replication.
Structure-based drug design has led to the identification of potent and selective inhibitors of influenza virus sialidase, which have antiviral activity in vitro and in experimental animal models of influenza infection. Clinical studies with one such sialidase inhibitor, zanamivir, have shown this compound to be a safe and effective therapy for influenza infections in man. Passage of influenza viruses in the presence of zanamivir in vitro has been shown to result in the selection of viruses with reduced sensitivity to this drug. To date, however, there have been no reports of the isolation of zanamivir-resistant viruses during clinical studies of this compound. Further application of structure-based drug design is yielding novel classes of potent inhibitors of influenza virus sialidase.
Enzyme Pharmacology Unit, Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
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Bethell
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Smith