Marcello, Alessandro and Loregian, Arianna and Cross, A. and Marsden, H.S. and Hirst, Timothy R. and Palu, Giorgio (1994) Specific inhibition of herpes virus replication by receptor-mediated entry of an antiviral peptide linked to Escherichia coli enterotoxin B subunit. Proceedings of the National Academy of Sciences of the United States of America, 91 (19). pp. 8994-8998. ISSN 0027-8424. (The full text of this publication is not available from this repository)
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Mimetic peptides capable of selectively disrupting protein-protein interactions represent potential therapeutic agents for inhibition of viral and cellular enzymes. This approach was first suggested by the observation that the peptide YAGAVVNDL, corresponding to the carboxyl-terminal 9 amino acids of the small subunit of ribonucleotide reductase of herpes simplex virus, specifically inhibited the viral enzyme in vitro. Evaluation and use of this peptide as a potential antiviral agent has, however, been thwarted by its failure to inhibit virus replication in vivo, presumably because the peptide is too large to enter eukaryotic cells unaided. Here, we show that the nontoxic B subunit of Escherichia coil heat-labile enterotoxin can be used as a recombinant carrier for the receptor-mediated delivery of YAGAVVNDL into virally infected cells. The resultant fusion protein specifically inhibited herpes simplex virus type 1 replication and ribonucleotide reductase activity in quiescent Vero cells. Preincubation of the fusion protein with soluble GM1 ganglioside abolished this antiviral effect, indicating that receptor-mediated binding to the target cell is necessary for its activity. This provides direct evidence of the usefulness of carrier-mediated delivery to evaluate the intracellular efficacy of a putative antiviral peptide.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences|
|Depositing User:||O.O. Odanye|
|Date Deposited:||07 Jul 2009 20:29|
|Last Modified:||19 Jun 2014 15:22|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/19877 (The current URI for this page, for reference purposes)|