3-O-galloylated procyanidins from Rumex acetosa L. inhibit the attachment of influenza A virus

Infections by influenza A viruses (IAV) are a major health burden to mankind. The current antiviral arsenal against IAV is limited and novel drugs are urgently required. Medicinal plants are known as an abundant source for bioactive compounds, including antiviral agents. The aim of the present study...

Authors: Derksen, Andrea
Hensel, Andreas
Hafezi, Wali
Herrmann, Fabian C.
Schmidt, Thomas J.
Ehrhardt, Christina
Ludwig, Stephan
Kühn, Joachim
Division/Institute:FB 13: Biologie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2014
Date of publication on miami:12.12.2014
Modification date:23.01.2020
Edition statement:[Electronic ed.]
Source:PLoS ONE 9 (2014) 10, 1-13, e110089
DDC Subject:570: Biowissenschaften; Biologie
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:1932-6203
URN:urn:nbn:de:hbz:6-81319562667
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-81319562667
Other Identifiers:DOI: doi:10.1371/journal.pone.0110089
Digital documents:journal.pone.0110089.pdf

Infections by influenza A viruses (IAV) are a major health burden to mankind. The current antiviral arsenal against IAV is limited and novel drugs are urgently required. Medicinal plants are known as an abundant source for bioactive compounds, including antiviral agents. The aim of the present study was to characterize the anti-IAV potential of a proanthocyanidin-enriched extract derived from the aerial parts of Rumex acetosa (RA), and to identify active compounds of RA, their mode of action, and structural features conferring anti-IAV activity. In a modified MTT (MTTIAV) assay, RA was shown to inhibit growth of the IAV strain PR8 (H1N1) and a clinical isolate of IAV(H1N1)pdm09 with a half-maximal inhibitory concentration (IC50) of 2.5 µg/mL and 2.2 µg/mL, and a selectivity index (SI) (half-maximal cytotoxic concentration (CC50)/IC50)) of 32 and 36, respectively. At RA concentrations>1 µg/mL plaque formation of IAV(H1N1)pdm09 was abrogated. RA was also active against an oseltamivir-resistant isolate of IAV(H1N1)pdm09. TNF-α and EGF-induced signal transduction in A549 cells was not affected by RA. The dimeric proanthocyanidin epicatechin-3-O-gallate-(4β→8)-epicatech​in-3′-O-gallate(procyanidin B2-di-gallate) was identified as the main active principle of RA (IC50 approx. 15 µM, SI≥13). RA and procyanidin B2-di-gallate blocked attachment of IAV and interfered with viral penetration at higher concentrations. Galloylation of the procyanidin core structure was shown to be a prerequisite for anti-IAV activity; o-trihydroxylation in the B-ring increased the anti-IAV activity. In silico docking studies indicated that procyanidin B2-di-gallate is able to interact with the receptor binding site of IAV(H1N1)pdm09 hemagglutinin (HA). In conclusion, the proanthocyanidin-enriched extract RA and its main active constituent procyanidin B2-di-gallate protect cells from IAV infection by inhibiting viral entry into the host cell. RA and procyanidin B2-di-gallate appear to be a promising expansion of the currently available anti-influenza agents.