Recent advances in neuraminidase inhibitor development as anti-influenza drugs

ChemMedChem. 2012 Sep;7(9):1527-36. doi: 10.1002/cmdc.201200155. Epub 2012 Jul 16.

Abstract

The recent emergence of the highly pathogenic H5N1 subtype of avian influenza virus (AIV) and of the new type of human influenza A (H1N1) have emphasized the need for the development of effective anti-influenza drugs. Presently, neuraminidase (NA) inhibitors are widely used in the treatment and prophylaxis of human influenza virus infection, and tremendous efforts have been made to develop more potent NA inhibitors to combat resistance and new influenza viruses. In this review, we discuss the structural characteristics of NA catalytic domains and the recent developments of new NA inhibitors using structure-based drug design strategies. These drugs include analogues of zanamivir, analogues of oseltamivir, analogues of peramivir, and analogues of aromatic carboxylic acid and present promising options for therapeutics or leads for further development of NA inhibitors that may be useful in the event of a future influenza pandemic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acids, Carbocyclic
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Benzoic Acid / chemistry
  • Benzoic Acid / pharmacology
  • Cyclopentanes / chemistry
  • Cyclopentanes / pharmacology
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Guanidines / chemistry
  • Guanidines / pharmacology
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Influenza A Virus, H5N1 Subtype / enzymology
  • Influenza, Human / drug therapy
  • Models, Molecular
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Neuraminidase / metabolism
  • Orthomyxoviridae / drug effects
  • Orthomyxoviridae / enzymology*
  • Orthomyxoviridae Infections / drug therapy
  • Oseltamivir / chemistry
  • Oseltamivir / pharmacology
  • Zanamivir / chemistry
  • Zanamivir / pharmacology

Substances

  • Acids, Carbocyclic
  • Antiviral Agents
  • Cyclopentanes
  • Enzyme Inhibitors
  • Guanidines
  • Oseltamivir
  • Benzoic Acid
  • Neuraminidase
  • Zanamivir
  • peramivir