Oligomeric proanthocyanidins from Rumex acetosa L. inhibit the attachment of herpes simplex virus type-1

The polyphenole-enriched acetone-water extract R2 from the aerial parts of Rumex acetosa L containing high amounts of oligomeric and polymeric proanthocyanidins and flavonoids was tested for antiviral activity. R2 exhibited strong antiviral activity against herpes simplex virus type-1 (HSV-1) while the replication of adenovirus 3 was not affected. By plaque reduction test and mu assay on Vero cells, the HSV-1-specific inhibitory concentration (IC50) and cytotoxic concentration (CC50) were determined. R2 exibited an IC50 of 0.8 mu g/mL and a selectivity index (SI) (ratio of IC50 to CC50) of approximately 100 when added to the virus inoculum for 1 h at 37 degrees C prior to infection. The antiviral activity was due to the presence of flavan-3-ols and oligomeric proanthocyanidins in the extract. Structure-activity analyses indicated that flavan-3-ols and proanthocyanidins with galloylation at position O-3 are highly potent compounds (SI > 40), while ungalloylated compounds did not exhibit antiviral effects (SI < 1). R2 and a major proanthocyanidin from R2, epicatechin-3-O-gallate-(4 beta --> 8)-epicatechin-3-O-gallate abolished virus entry into the host cell by blocking attachment to the cell surface. When added after attachment at a concentration of >= 12.5 mu g/mL, R2 inhibited also penetration of HSV-1 into the host cell. R2 and epicatechin-3-O-gallate-(4 beta --> 8)-epicatechin-3-O-gallate were shown to directly interact with viral particles leading to the oligomerisation of envelope proteins as demonstrated for the essential viral glycoprotein gD. Using raft cultures with three-dimensional organotypic human skin equivalents it was shown that treatment of cultures with R2 after infection with HSV-1 resulted in a reduced viral spread. (C) 2010 Elsevier B.V. All rights reserved.