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Protease Inhibitors Prevent the Development of Human Rotavirus‐Induced Diarrhea in Suckling Mice
Author(s) -
Ebina Takusaburo,
Tsukada Keiko
Publication year - 1991
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1991.tb01589.x
Subject(s) - diarrhea , rotavirus , infectivity , protease , biology , protease inhibitor (pharmacology) , virology , oral administration , proteases , reoviridae , cysteine protease , serine protease , microbiology and biotechnology , virus , pharmacology , medicine , enzyme , viral load , biochemistry , antiretroviral therapy
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 mgx2), 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.