The synthesis and biological evaluation of lactose-based sialylmimetics as inhibitors of rotaviral infection.
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.
Liakatos
Angela
A
Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Qld 9726, Australia.
Kiefel
Milton J
MJ
Fleming
Fiona
F
Coulson
Barbara
B
von Itzstein
Mark
M
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
D000998:Antiviral Agents; D006027:Glycosides; D012794:Sialic Acids; C008245:lactosides; D007785:Lactose