'Flu' and structure-based drug design.
The threat of a catastrophic outbreak of influenza is ever present. Vaccines are only partially effective and the two compounds, amantidine and rimantidine, used clinically against influenza A cause side-effects and rapid viral resistance. Recent advances bring hope that specific and potent drugs against influenza may soon be available in the clinic. These compounds were designed to inhibit influenza neuraminidase (NA), one of the viral coat glycoproteins, using the crystal structure of NA which was first published in 1983. In this review, the application of structure-based drug design approaches to the design of anti-influenza agents targeted at NA and haemagglutinin (HA), the other viral surface glycoprotein, is discussed.
Wade
R C
RC
Structural Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany. wade@embl-heidelberg.de
D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy*; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D053139:Oseltamivir; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology / Q000627:therapeutic use; D053243:Zanamivir
D000588:Amines; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir