title: 4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro.
abstract: The sialidase (neuraminidase) inhibitor 4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid (4-guanidino-Neu5Ac2en) has been examined for the ability to inhibit the growth of a wide range of influenza A and B viruses in vitro in comparison with amantadine, rimantadine, and ribavirin. 4-Guanidino-Neu5Ac2en inhibited plaque formation by laboratory-passaged strains of influenza A and B viruses, with 50% inhibitory concentrations ranging from 0.005 to 0.014 microM. A wider range of values (0.02 to 16 microM) was obtained with more recent clinical isolates, but in all cases 4-guanidino-Neu5Ac2en inhibited influenza A and B virus replication at lower concentrations than amantadine, rimantadine, or ribavirin. Inhibition by 4-guanidino-Neu5Ac2en was not obviously affected by the passage history of the viruses or by resistance to amantadine or rimantadine. 4-Guanidino-Neu5Ac2en was a very potent inhibitor of the sialidases of all the influenza viruses examined, with 50% inhibitory concentrations ranging from 0.00064 to 0.0079 microM. No cytotoxicity was observed with 4-guanidino-Neu5Ac2en at up to 10 mM. 4-Guanidino-Neu5Ac2en therefore represents a new potent and selective inhibitor of influenza A and B virus sialidase activity and replication in vitro.
authors.affiliation: Department of Virology, Glaxo Group Research Limited, Greenford, Middlesex, United Kingdom.
authors.forename: J M
authors.initials: JM
authors.lastname: Woods
authors.forename: R C
authors.initials: RC
authors.lastname: Bethell
authors.forename: J A
authors.initials: JA
authors.lastname: Coates
authors.forename: N
authors.initials: N
authors.lastname: Healy
authors.forename: S A
authors.initials: SA
authors.lastname: Hiscox
authors.forename: B A
authors.initials: BA
authors.lastname: Pearson
authors.forename: D M
authors.initials: DM
authors.lastname: Ryan
authors.forename: J
authors.initials: J
authors.lastname: Ticehurst
authors.forename: J
authors.initials: J
authors.lastname: Tilling
authors.forename: S M
authors.initials: SM
authors.lastname: Walcott
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007251:Influenza, Human / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology* / Q000633:toxicity; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir
chemical_list: D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D014316:Tritium; D009439:Neuraminidase; D053243:Zanamivir; D013936:Thymidine