Antiviral activity of theaflavin digallate against herpes simplex virus type 1

Antiviral Res. 2015 Jun:118:56-67. doi: 10.1016/j.antiviral.2015.03.009. Epub 2015 Mar 27.


Tea is the second most consumed drink in the world. The beneficial effects of tea have been mostly attributed to its catechin content. Black tea is derived from the leaves of Camellia sinensis plant, and it is rich in theaflavin polyphenols, in particular theaflavin (TF1), theaflavin-3-monogallate (TF2A), theaflavin-3'-monogallate (TF2B), and theaflavin-3,3'-digallate (TF3). Vero and A549 cells were used to evaluate the effect of purified individual black tea theaflavins as anti-herpes simplex virus 1 agents. With the rise of HSV resistant strains, there is a critical need to develop novel antiherpesviral treatments. Results of the cytotoxicity assay tested by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] showed that TF1, TF2, and TF3 are not toxic to Vero and A549 cells at a concentration up to 75 μM. The antiviral activity of the individual theaflavins was tested by plaque reduction assay, MTS assay, flow cytometric analysis and confocal microscopy observations. The results showed that TF1, TF2, and TF3 exhibit potent, dose-dependent anti-HSV-1 effect, with TF3 being the most efficient in both Vero and A549 cells. A concentration of 50 μM TF3 and above was sufficient to inhibit >99% of the production of HSV-1 viral particles. The anti-HSV-1 effect of TF3 is due to a direct effect on the virions, and treating Vero or A549 cells with TF3 for 1h prior to infection, or treating the cells at different times post infection does not inhibit HSV-1 production. TF3 is stable at vaginal pH, indicating its potential to be a promising natural and affordable remedy against herpes simplex viral infections.

Keywords: A549 cells; HSV-1; Herpes simplex virus; Natural product; Theaflavins; Vero cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biflavonoids / isolation & purification
  • Biflavonoids / pharmacology*
  • Biflavonoids / toxicity
  • Biological Products / isolation & purification
  • Biological Products / pharmacology*
  • Biological Products / toxicity
  • Camellia sinensis / chemistry*
  • Catechin / isolation & purification
  • Catechin / pharmacology*
  • Catechin / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Disinfectants / isolation & purification
  • Disinfectants / pharmacology*
  • Disinfectants / toxicity
  • Epithelial Cells / drug effects
  • Flow Cytometry
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / isolation & purification
  • Gallic Acid / pharmacology
  • Gallic Acid / toxicity
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / physiology
  • Humans
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects*
  • Microscopy, Confocal
  • Staining and Labeling
  • Viral Plaque Assay
  • Virus Inactivation*


  • Biflavonoids
  • Biological Products
  • Disinfectants
  • theaflavin digallate
  • Gallic Acid
  • Catechin