Controlling influenza by inhibiting the virus's neuraminidase.
Despite the fact that influenza is a disease which affects millions of people, sometimes with fatal consequences. there has not, until recently, been any drug effective against all strains. Vaccines may be relatively or totally ineffective, so drugs are needed. Random screening of many thousands of compounds by pharmaceutical companies has resulted in only two compounds, amantadine and rimantidine, which target the M2 ion channel on the virus. These drugs have major disadvantages. Knowledge of the crystal structure of influenza virus neuraminidase, on the other hand, has allowed the rational design of four "plug-drugs" which bind to the active site of flu neuraminidase and stop replication of the virus. Two of these compounds. Relenza and Tamiflu, are now being used worldwide and, although effective when used properly, suffer from problems of delivery. They need to be given very soon after infection to be effective, they only inhibit the influenza virus and none of the other respiratory agents which cause flu-like symptoms, and they are very expensive.
Garman
Elspeth
E
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. elspeth@biop.ox.ac.uk
Laver
Graeme
G
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006388:Hemagglutinins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D007473:Ion Channels / Q000037:antagonists & inhibitors; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009975:Orthomyxoviridae / Q000201:enzymology*; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006388:Hemagglutinins; D007473:Ion Channels; D014760:Viral Fusion Proteins; D009439:Neuraminidase