Slow-binding inhibition of sialidase from influenza virus.
Sialidase from influenza virus A (Tokyo/3/67, N2) is inhibited in slow-binding fashion by 2,3-didehydro-2,4-dideoxy-4-guanidino-N-acetyl-D-neuraminic acid. The Ki observed for the tightly-bound form at steady-state is 3 x 10(-11) M. Slow-binding, which is a consequence of the guanidinyl moiety of the inhibitor, is observed only for influenza virus A sialidase and not for influenza virus B or any other viral, bacterial, or mammalian sialidase investigated. The different results obtained for sialidases from influenza virus A and B, whose active sites are conserved, point to the involvement of the expulsion of a structural water molecule in the slow-binding mechanism.
Pegg
M S
MS
School of Pharmaceutical Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Australia.
von Itzstein
M
M
D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D006146:Guanidines; D009980:Influenza A virus / Q000201:enzymology*; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011714:Pyrans; D012794:Sialic Acids / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014867:Water / Q000737:chemistry; D053243:Zanamivir
D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D014867:Water; D009439:Neuraminidase; D053243:Zanamivir