Tannins from Hamamelis virginiana Bark Extract: Characterization and Improvement of the Antiviral Efficacy against Influenza A Virus and Human Papillomavirus

Abstract

Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals.

High-throughput screening for the identification of small-molecule inhibitors of the flaviviral protease

“…It is also used orally for bleeding, chronic diarrhea, dysentery, bloody urine, painful joints and persistent coughs (Chung et al, 1998). Antiviral activities have been demonstrated for at least twelve different viruses: influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus, Newcastle disease virus, poliovirus, coxsackievirus, adenovirus, rotavirus, feline calicivirus, human papillomavirus, and mouse norovirus (Buzzini et al, 2008; Theisen et al, 2014; Ueda et al, 2013). More importantly, previous studies have shown that hydrolysable tannins, chebulagic acid and punicalagin protect against dengue virus infections (Lin et al, 2013).…”

Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid

“…In addition, the therapeutic safety of gallic acid was found to be lower than other hydrolysable tannins and pseudotannins. 25 In this study, we found that both of these two compounds indeed exerted anti-influenza A (H1N1) virus replication via significant inhibition of viral RNA synthesis. Meanwhile, catechin and gallic acid were shown to inhibit the growth of pandemic influenza A (H1N1) with EC50 of 18.4 mg/mL and 2.6 mg/mL in MDCK cells, and SI of >5.6 and 8.6, respectively.…”

“…24 Theisen et al reported the cytotoxic and antiviral activities against H1N1 virus (H1N1 A/Puerto Rico/8/ 34-NS116-GFP) of gallic acid with CC 50 , EC 50 and SI were 770.5 mM, 50.8 mM, and 15.2 mM, respectively, which differs from the results reported from the present study. 25 This could possibly result from the different viral strains used in experimentation. In addition, the therapeutic safety of gallic acid was found to be lower than other hydrolysable tannins and pseudotannins.…”

Tannins as Antiviral Agents

“…Of the investigated substances high molecular weight tannin inhibited both IAV receptor binding and neuraminidase activity. However, those with low molecular weight tannin inhibited neuraminidase but not hemagglutination [36].…”