Strain-specific antiviral activity of iminosugars against human influenza A viruses

Results: The inhibitors had the strongest effect on Brisbane/10 and NN-DNJ was more potent than NB-DNJ. Both compounds showed antiviral activity in cell culture against three human influenza A viruses in a strain-specific manner. Consistent with its action as an a-glucosidase inhibitor, NN-DNJ treatment resulted in an altered glycan processing of influenza haemagglutinin (HA) and neuraminidase (NA), confirmed by MS. NN-DNJ treatment was found to reduce the cell surface expression of the H3 subtype HA. The level of sialidase activityof NAwas reduced in infected cells, but the addition of exogenous sialidase to the cells did not complement the NN-DNJ-mediated inhibition ofvirusreplication. Usingreassortant viruses,thedrugsusceptibilityprofilewasdeterminedtocorrelate with the origin of the HA. Conclusions:NN-DNJ inhibits influenza Avirus replication in a strain-specific manner that is dependent onthe HA.