Inhibition of Rotavirus Infectivity by a Neoglycolipid Receptor Mimetic

Nutrients

Daniel W. Bergner²  Theresa B. Kuhlenschmidt³  William P. Hanafin¹  Lawrence D. Firkins³ 

[1] Institute for Genomic Biology, University of Illinois, 1206 West Gregory Drive, Urbana, IL 61801, USA;Department of Medicine, Feinberg School of Medicine, Northwestern University, 420 East Superior Street, Chicago, IL 60611, USA;Department of Pathobiology, College of Veterinary Medicine, University of Illinois, 2001 South Lincoln Avenue, Urbana, IL 61802, USA;

关键词: nutriceutical;    carbomimetic;    receptor therapy;    neoglycolipid;    rotavirus;    ganglioside;    infectious;    disease;   

DOI  :  10.3390/nu3020228

来源: mdpi

【 摘 要 】

Group A rotaviruses are a major cause of diarrhea in the young of many mammalian species. In rotavirus infected piglets mortality can be as high as 60%. Previous research in this laboratory has identified a porcine intestinal GM₃ ganglioside receptor that is required for sialic acid-dependent rotavirus recognition of host cells. In addition, we previously demonstrated exogenously added GM₃ can competitively inhibit porcine rotavirus binding and infectivity of host cells in vitro. Sialyllactose, the carbohydrate moiety of GM₃, is approximately 3 orders of magnitude less effective than GM₃ at inhibiting rotavirus binding to cells. Furthermore, production of therapeutic quantities of GM₃ ganglioside for use as an oral carbomimetic in swine is cost prohibitive. In an effort to circumvent these problems, a sialyllactose-containing neoglycolipid was synthesized and evaluated for its ability to inhibit rotavirus binding and infectivity of host cells. Sialyllactose was coupled to dipalmitoylphosphatidylethanolamine (PE) by reductive amination and the product (SLPE) purified by HPLC. Characterization of the product showed a single primulin (lipid) and resorcinol (sialic acid) positive band by thin layer chromatography and quantification of phosphate and sialic acid yielded a 1:1 molar ratio. Mass spectroscopy confirmed a molecular weight coinciding with SLPE. Concentration-dependent binding of rotavirus to SLPE was demonstrated using a thin-layer overlay assay. Using concentrations comparable to GM₃, SLPE was also shown to inhibit rotavirus binding to host cells by 80%. Furthermore, SLPE was shown to decrease rotavirus infection of host cells by over 90%. Finally, preliminary results of in vivo animal challenge studies using newborn piglets in their natural environment, demonstrated SLPE afforded complete protection from rotavirus disease. The efficacy of SLPE in inhibiting rotavirus binding and infection in vitro and in vivo, coupled with its relatively low-cost, large-scale production capabilities make SLPE a promising candidate for further exploration as a possible prophylactic or therapeutic nutriceutical for combating rotavirus disease in animals. Most importantly, the results presented here provide proof of concept that the nutriceutical approach of providing natural or synthetic dietary receptor mimetics for protection against gastrointestinal virus infectious disease in all species is plausible.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.