AIDSWEEKLY Plus; Monday, September 1, 2003
Staff Medical Writers

According to a study from Germany, "N,N'-bisheteryl derivatives of dispirotripiperazine (DSTP) are a novel class of antiviral compounds with some of their representatives very effectively inhibiting the replication of herpes simplex virus type 1 (HSV-1) in cell culture."

"Using one representative of these compounds, the N,N'-bis(1-oxido[1,2,5]oxadiazolo[3,4-d]pyrimidin-7-yl)-3,12-diaza-6,9-diazonia(5,2,5,2)dispirohexadecane dichloride (DSTP 27)," M. Schmidtke and coauthors at the University of Jena "further tried to elucidate the molecular mechanisms responsible for the antiviral activity."

"The results from plaque reduction assays under a variety of conditions suggest that inhibition of HSV-1 strain Kupka replication by DSTP 27 occurs at the level of viral attachment by blockade of heparan sulfate (HS) structures on the cell surface that are used as viral receptors," they reported.

"In contrast to heparin and pentosan polysulfate, pretreatment of cells with DSTP 27 resulted in efficient inhibition of viral adsorption and replication persisting several hours after removal of the inhibitor," study data revealed. "Specific binding of DSTP 27 to heparin was demonstrated in vitro. Titrations of gC-positive and gC-negative pseudorabies virus (PrV) mutants on HS-positive and HS-negative cell lines confirmed that inhibitory action of DSTP 27 is strictly HS dependent."

"Aside from HSV-1 Kupka and PrV, DSTP 27 efficiently inhibits growth of several HSV-1 and HSV-2 strains, among them aciclovir/foscarnet-resistant strains, human cytomegalovirus, human respiratory syncytial virus, and human immunodeficiency viruses known to attach to the cell surface via HS," the researchers concluded.

Schmidtke and colleagues published the results of their research in Virology (Binding of a N,N'-bisheteryl derivative of dispirotripiperazine to heparan sulfate residues on the cell surface specifically prevents infection of viruses from different families. Virology. 2003 Jun 20;311(1):134-43.

For additional information, contact M. Schmidtke, University of Jena, Institute for Virology and Antiviral Therapy, Winzerlaer Str. 10, D-07745 Jena, Germany.

The publisher of the journal Virology can be contacted at: Academic Press Inc., Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA.

The information in this article comes under the major subject areas of AIDS & HIV, Herpesvirus, Infectious Disease, Pharmaceutical & Drug Development and Virology.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Schmidtke M, Karger A, Meerbach A, et al., "Binding of a N,N'-bisheteryl derivative of dispirotripiperazine to heparan sulfate residues on the cell surface specifically prevents infection of viruses from different families", Virology. 2003 Jun 20;311(1):134-43.

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