PMID: 16535861Mar 16, 2006Paper

Neuraminidase inhibitors as antiviral agents

Current Drug Targets. Infectious Disorders
Irina V AlymovaAllen Portner

Abstract

The enzyme neuraminidase (NA) is an attractive target for antiviral strategy because of its essential role in the pathogenicity of many respiratory viruses. NA removes sialic acid from the surface of infected cells and virus particles, thereby preventing viral self-aggregation and promoting efficient viral spread; NA also plays a role in the initial penetration of the mucosal lining of the respiratory tract. Random screening for inhibitors has identified only low-affinity and nonselective viral NA inhibitors. Selective, high-affinity inhibitors of influenza virus neuraminidase, zanamivir and oseltamivir, were developed using computer-aided design techniques on the basis of the three-dimensional structure of the influenza virus NA. These drugs were highly efficient in inhibiting replication of both influenza A and B viruses in vitro and in vivo and were approved for human use in 1999. Subsequently, the same structure-based design approach was used for the rational design of inhibitors of the parainfluenza virus hemagglutinin-neuraminidase (HN). One of these compounds, BCX 2798, effectively inhibited NA activity, cell binding, and growth of parainfluenza viruses in tissue culture and in the lungs of infected mice. Clinical report...Continue Reading

Citations

Sep 30, 2006·Journal of Computer-aided Molecular Design·Theodora M SteindlThierry Langer
May 15, 2013·Veterinary Microbiology·Timothy H HyndmanRachel E Marschang
Jun 6, 2009·Journal of Virology·Thomas A BowdenDavid I Stuart
Nov 23, 2007·Journal of the American Pharmacists Association : JAPhA·Aleksander P WiniarskiKathy Nagano-Mate
Nov 6, 2013·FEMS Microbiology Reviews·Wander Van BreedamHans J Nauwynck
Feb 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anthony G VecchiarelliKiyoshi Mizuuchi
Sep 25, 2007·American Journal of Therapeutics·Mario GuralnikCarolyn Lefante

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