Abstract
Rotavirus is a major cause of gastrointestinal disease in humans. Rotaviruses replicate in the gastrointestinal tract and their growth is stimulated by gastrointestinal proteases. We investigated the ability of protease inhibitors to prevent rotavirus replication both in the presence and absence of exogenous proteases. We evaluated macromolecular protease inhibitors including alpha-1 anti-trypsin, soy protease inhibitor, and egg white inhibitor as well as low molecular weight inhibitors such as bestatin, pepstatin, and bis-(5 amidino-2-benzimidazolyl) methane (BABIM). All of the protease inhibitors demonstrated in vitro efficacy against rotavirus as determined by the inhibition of replication of cultivatable rotavirus strains in primary cell lines. Efficacy was noted both in the presence and absence of added proteases. In addition, BABIM was found to inhibit the replication of murine rotavirus in orally infected mice. The drug could be administered orally or parenterally and was without toxic effects at effective doses. The other protease inhibitors demonstrated lower levels of in vivo efficacy. BABIM is a protease inhibitor which is capable of preventing the in vivo and in vitro replication of rotavirus. This drug and other protease inhibitors might have efficacy for the prevention and treatment of human infection with rotaviruses and other protease requiring viruses.
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Yolken, R., Eiden, J., Vonderfecht, S. et al. 1182 PROTEASE ANATAGONISTS INHIBIT THE IN VIVO AND IN VITRO REPLICATION OF ROTAVIRUS. Pediatr Res 19, 307 (1985). https://doi.org/10.1203/00006450-198504000-01212
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DOI: https://doi.org/10.1203/00006450-198504000-01212