title: The synthesis and biological evaluation of lactose-based sialylmimetics as inhibitors of rotaviral infection.
abstract: Rotaviruses are the most significant cause of gastroenteritis in young children and are responsible for over 600,000 infant deaths annually. The rotaviral haemagglutinin protein (VP8*) of some strains has been implicated in early recognition and binding events of host cell-surface sialoglycoconjugates, and is therefore an attractive target for potential therapeutic intervention. Since N-acetylneuraminic acid alpha(2,3)-linked to galactose is believed to be the minimum binding epitope of rotavirus to host cells, we report here our development of an efficient and flexible synthetic route to a range of lactose-based sialylmimetics of alpha(2,3)-linked thiosialosides. These compounds were biologically evaluated as inhibitors of rotaviral infection using an in vitro neutralisation assay. The results suggest that these lactose-based sialylmimetics are not inhibitors of the rhesus rotavirus strain; however, they do exhibit modest inhibition of the human (Wa) strain, presumably through inhibition of the rotaviral adhesion process.
authors.affiliation: Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Qld 9726, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Liakatos
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Kiefel
authors.forename: Fiona
authors.initials: F
authors.lastname: Fleming
authors.forename: Barbara
authors.initials: B
authors.lastname: Coulson
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012401:Rotavirus / Q000187:drug effects*; D012400:Rotavirus Infections / Q000188:drug therapy; D012794:Sialic Acids / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D006027:Glycosides; D012794:Sialic Acids; C008245:lactosides; D007785:Lactose