Structure–activity relationships of saponin derivatives: A series of entry inhibitors for highly pathogenic H5N1 influenza virus

The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Theoretically, each of steps in influenza viral life cycle can be a target of antiviral therapeutics. However, up to date, no licenced entry inhibitor drug is available for H5N1 or any other influenza viruses. Our strategy for developing new anti-influenza therapeutics is to target the interaction between HA and sialic acid which is influenza viral receptor presented on host cell surface. Here, based on our previously discovered small molecule inhibitor saponin 1, intensive SAR studies around the sugar chain and aglycone were conducted. The results showed that both the chacotriosyl residue and the chlorogenin moiety of active compound 1 are important for the antiviral activity, although several subtle modifications can be made on particular positions.

Intensive SAR studies around the sugar chain and aglycone were conducted on highly pathogenic H5N1 influenza viral entry inhibitory activity.Figure optionsDownload as PowerPoint slideHighlights
► Saponin derivatives were discovered as small molecule H5N1 viral entry inhibitors.
► Intensive SAR studies around the sugar chain and aglycone of the saponin derivatives were conducted.
► Both the chacotriosyl and chlorogenin moiety of active compound 1 are important for the antiviral activity.