Protease inhibitors prevent the development of human rotavirus-induced diarrhea in suckling mice.
Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice caused gastroenteritis characterized by diarrhea (90% on the average, on day 2). Using this animal model, preventive effect of antiviral agents on the development of rotavirus-induced diarrhea was examined. The infectivity of human rotavirus was enhanced by treatment with protease in vitro. A cysteine protease inhibitor, E-64-c, was given orally at 12 hr and 24 hr after MO infection. Oral administration of 0.3 mg of E-64-c decreased the diarrhea ratio to 17.5% on day 2 and to 10% on day 3. Oral administration of 0.15 mg of cysteine protease inhibitor, ovocystatin, completely prevented the diarrhea on day 2. Serine protease inhibitor, aprotinin (0.15 mg x 2), also prevented the diarrhea on day 2 to 14.3%. These protease inhibitors were nontoxic in vitro and to suckling mice. The histopathological changes in the small intestine due to infection recovered 2 days after MO infection in mice treated with E-64-c and ovocystatin. These results suggest that protease inhibitors are protective agents for human rotavirus infection by inhibiting proteases required for viral replication.
Ebina
T
T
Department of Bacteriology, Tohoku University School of Medicine, Miyagi.
Tsukada
K
K
D000284:Administration, Oral; D000818:Animals; D000833:Animals, Suckling; D007611:Aprotinin / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives*; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D003967:Diarrhea / Q000517:prevention & control*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012401:Rotavirus / Q000187:drug effects; D012400:Rotavirus Infections / Q000188:drug therapy* / Q000382:microbiology; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use
D015853:Cysteine Proteinase Inhibitors; D005419:Flavonoids; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D002392:Catechin; D007611:Aprotinin; C057580:gallocatechol