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 The sialidase (neuraminidase, acylneuraminyl hydrolase, EC 3.2

Efficacy and Safety of the Neuraminidase Inhibitor Zanamivir in the Treatment of Influenzavirus Infections

“…The magnitude of the clinical benefit observed in this study appears to be at least as great as that in earlier trials of amantadine and rimantadine for acute febrile influenza A illness in adults. [17][18][19][20] In addition, as predicted by the results of in vitro studies, 8,9 tests in animal models, 8,10 and experimental studies in humans, 21 the antiviral spectrum and clinical effectiveness of zanamivir included influenza B virus infections.…”

“…6,7 Zanamivir inhibits a range of influenza A and B viruses in vitro. 8,9 Topically applied zanamivir is active in animal models of influenza, 3,8,10 although systemically administered drug has little antiviral activity. In adults experimentally inoculated with influenza A virus, prophylactic intranasal zanamivir was highly protective against infection and febrile illness.…”

In Vitro Efficacies of Oseltamivir Carboxylate and Zanamivir against Equine Influenza A Viruses

“…To clarify the reason for the phenomenon observed in Italy91, further investigation on the HA gene of Italy91 would be necessary. However, since the human strains with reduced susceptibility to ZA in cell culture were shown to be sensitive to ZA in vivo [12,15], it is difficult to conclude that Italy91 is less susceptible to OC or ZA in vivo than the other EIVs from this limited study.…”

“…Although the IC 50 s of OC and ZA for Italy91 were almost similar to those for the other EIVs examined in this study, the EC 50 s of both compounds for the virus were at least 75 times higher than those for the other EIVs. This phenomenon was observed in some human influenza A viruses [5,6,12,15]. Studies on human strains with reduced susceptibility to ZA in PRA showed that the resistance could be associated with mutations in the HA gene, and that a weaker affinity of the HA for the cellular receptors by HA mutations would allow release of virus from infected cells even in the presence of a NA inhibitor [5,6,12].…”

“…To evaluate the effective efficacies of OC and ZA against the replications of EIVs, plaque reduction assays (PRAs) were performed as described previously with some modifications [15]. Monolayers of MDCK cells in 6-well culture plate were inoculated with EIV diluted in Eagle's minimal essential medium (EMEM) containing 2.0 μg/ml of acety- lated trypsin to give 50 to 100 plaques per well.…”