Influenza hemagglutinin and neuraminidase membrane glycoproteins.
Considerable progress has been made toward understanding the structural basis of the interaction of the two major surface glycoproteins of influenza A virus with their common ligand/substrate: carbohydrate chains terminating in sialic acid. The specificity of virus attachment to target cells is mediated by hemagglutinin, which acquires characteristic changes in its receptor-binding site to switch its host from avian species to humans. Anti-influenza drugs mimic the natural sialic acid substrate of the virus neuraminidase enzyme but utilize the much tighter binding of the drugs for efficacy. Resistance to one of the two main antiviral drugs is differentially acquired by the two distinct subsets of neuraminidase as a consequence of structural differences in the enzyme active site between the two phylogenetic groups.
Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. sgambli@nimr.mrc.ac.uk
Steven J
SJ
Gamblin
John J
JJ
Skehel
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000502:physiology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology*; D007251:Influenza, Human / Q000188:drug therapy / Q000201:enzymology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D053585:Virus Attachment / Q000187:drug effects
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid