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Antimicrobial Agents and Chemotherapy, February 2002, p. 420-424, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.420-424.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Protective Efficacy of a Sulfated Sialyl Lipid (NMSO3) against Human Rotavirus-Induced Diarrhea in a Mouse Model

Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima,¹ Department of VirologyParasitology, Fujita Health University School of Medicine, Toyoake, Aichi,² Division of Immunology, Miyagi Cancer Center Research Institute, Natori, Miyagi,³ Department of Microbiology, Akita University, Akita,⁴ Nissin Food Products Co. Ltd., Central Research Institute, Kusatsu, Shiga, Japan⁵

Received 25 January 2001/ Returned for modification 30 April 2001/ Accepted 23 October 2001

Antiviral activity of sulfated sialyl lipid (NMSO3) against human rotavirus (RV) was examined in vitro and in vivo. NMSO3 inhibited the replication of four major serotypes (G1 to G4) of human rotavirus with a low 50% effective concentration of 1 to 5 µg/ml and 50% cytotoxic concentration of 153 µg/ml when determined by plaque assays with MA104 cells. Exposure of NMSO3 to HCl (pH 2.0) for 30 min exhibited no loss of anti-RV activity. Time-of-addition experiments revealed that NMSO3 inhibited the adsorption of four serotypes of RV to MA104 cells. Furthermore, an assay of virus binding with radiolabeled RVs revealed that NMSO3 inhibited the binding of virus to MA104 cells, suggesting that NMSO3 may bind to VP4 and/or VP7. Prophylactic oral administration of NMSO3 (10 µg three times per day, 4 days) to five suckling mice starting 30 min before inoculation of MO strain (3 x 10⁶ PFU/mouse) prevented the development of diarrhea. Four of five mice showed no stool or brown formed stool, and only one mouse showed brown soft stool, while water treatment caused watery diarrhea in all five mice. The mean titer of antibody to RV in mice which received NMSO3 at 10 µg three times per day for 4 days was significantly lower than that of untreated, infected mice. NMSO3 is a promising candidate for the prophylactic treatment of human RVs.

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