The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design.
Nature
; 443(7107): 45-9, 2006 Sep 07.
Article
in En
| MEDLINE
| ID: mdl-16915235
ABSTRACT
The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.
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Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Design
/
Influenza A Virus, H5N1 Subtype
/
Influenza in Birds
/
Neuraminidase
Limits:
Animals
/
Humans
Language:
En
Journal:
Nature
Year:
2006
Type:
Article
Affiliation country:
United kingdom