Rational design of potent sialidase-based inhibitors of influenza virus replication.
Two potent inhibitors based on the crystal structure of influenza virus sialidase have been designed. These compounds are effective inhibitors not only of the enzyme, but also of the virus in cell culture and in animal models. The results provide an example of the power of rational, computer-assisted drug design, as well as indicating significant progress in the development of a new therapeutic or prophylactic treatment for influenza infection.
von Itzstein
M
M
Department of Pharmaceutical Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Wu
W Y
WY
Kok
G B
GB
Pegg
M S
MS
Dyason
J C
JC
Jin
B
B
Van Phan
T
T
Smythe
M L
ML
White
H F
HF
Oliver
S W
SW
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D017076:Computer-Aided Design; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D005289:Ferrets; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011714:Pyrans; D012756:Sheep; D012794:Sialic Acids / Q000737:chemistry / Q000494:pharmacology*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir
D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; C081427:4-amino-2-deoxy-2,3-didehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D053243:Zanamivir