title: Structure-activity relationships of saponin derivatives: a series of entry inhibitors for highly pathogenic H5N1 influenza virus.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Sumei
authors.initials: S
authors.lastname: Ren
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
mesh_terms: D000107:Acetylation; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D020128:Inhibitory Concentration 50; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012503:Saponins