A protein-based therapeutic for human cytomegalovirus infection

François Jean, Laurel Thomas, Sean S. Molloy, Gseping Liu, Michael A. Jarvis, Jay A. Nelson, Gary Thomas

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Current antiviral strategies target viral gene products. Although initially successful, their severe toxicity and susceptibility to circumvention by the generation of drug-resistant variants limit their usefulness. By contrast, the central role of the host cell serine endoprotease furin in the proteolytic activation of numerous pathogens points to the endoprotease as a strategic target for therapeutics. Herein, we show that the production of infectious human cytomegalovirus is dramatically reduced by exogenous addition of a bioengineered serpin, α1-PDX. This protein is a potent and selective furin inhibitor (K(i) = 0.6 nM) and is 10- fold more effective than currently used antiherpetic agents in cell-culture models. The requirement of furin for the processing of envelope glycoproteins from many pathogenic viruses and for the activation of several bacterial toxins suggests that selective inhibitors of furin have potential as broad- based anti-pathogens.

Original languageEnglish (US)
Pages (from-to)2864-2869
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number6
DOIs
StatePublished - Mar 14 2000

ASJC Scopus subject areas

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