Protease inhibitors suppress the in vitro and in vivo replication of rotavirus

S. L. Vonderfecht, R. L. Miskuff, S. B. Wee, S. Sato, R. R. Tidwell, J. D. Geratz, R. H. Yolken

Research output: Contribution to journalArticle

Abstract

Rotaviruses are major causes of infectious gastoenteritis in humans and other animals. We found that a variety of protease inhibitors suppressed the replications of the SA-11 strain of rotavirus in MA-104 cell cultures. Three of these compounds, leupeptin, pentamidine, and bis (5-amidino-2-benzimidazolyl) methane (BABIM) also restricted the intestinal replication of the murine strain of rotavirus when protease inhibitor and virus were administered simultaneously to suckling mice. Repeated administration of BABIM resulted in significantly reduced levels of intestinal rotaviral antigen even if administration of the compound was begun as late as 48 h after viral inoculation. Additionally, BABIM-treated animals had significantly less intestinal replication of rotavirus than did placebo-treated controls when placed in a heavily rotavirus-contaminated environment. The use of protease inhibitors represents a novel approach to the control of this important gastrointestinal pathogen and is a potential modality for the prevention and treatment of diseases caused by other enteric viruses, for which proteolytic cleavage is necessary for efficient replication.

Original languageEnglish (US)
Pages (from-to)2011-2016
Number of pages6
JournalJournal of Clinical Investigation
Volume82
Issue number6
DOIs
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Medicine(all)

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    Vonderfecht, S. L., Miskuff, R. L., Wee, S. B., Sato, S., Tidwell, R. R., Geratz, J. D., & Yolken, R. H. (1988). Protease inhibitors suppress the in vitro and in vivo replication of rotavirus. Journal of Clinical Investigation, 82(6), 2011-2016. https://doi.org/10.1172/JCI113821