title: Antiviral activity of theaflavin digallate against herpes simplex virus type 1.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA.
authors.forename: Aline
authors.initials: A
authors.lastname: de Oliveira
authors.affiliation: Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Prince
authors.affiliation: Department of Food Science, National Chiayi University, Chiayi City, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lo
authors.affiliation: Department of Biology & Molecular Biology, Montclair State University, Montclair, NJ, USA.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA. Electronic address: Tin-Chun.Chu@shu.edu.
authors.forename: Tin-Chun
authors.initials: TC
authors.lastname: Chu
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004202:Disinfectants / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D018613:Microscopy, Confocal; D013194:Staining and Labeling; D010948:Viral Plaque Assay; D038301:Virus Inactivation
chemical_list: D044946:Biflavonoids; D001688:Biological Products; D004202:Disinfectants; C077197:theaflavin digallate; D005707:Gallic Acid; D002392:Catechin
keywords: A549 cells; HSV-1; Herpes simplex virus; Natural product; Theaflavins; Vero cells
references.citation: Antiviral Res. 2004 Feb;61(2):73-81
references.pmid: 14670580
references.citation: Mol Nutr Food Res. 2006 Dec;50(12):1118-28
references.pmid: 17103374
references.citation: Vet Microbiol. 1998 Oct;63(2-4):147-57
references.pmid: 9850995
references.citation: Antiviral Res. 2012 Jun;94(3):217-24
references.pmid: 22521753
references.citation: BMC Complement Altern Med. 2013 Jun 18;13:139
references.pmid: 23777309
references.citation: J Nutr Biochem. 2001 Jul;12(7):404-421
references.pmid: 11448616
references.citation: Clin Microbiol Rev. 2003 Jan;16(1):114-28
references.pmid: 12525428
references.citation: Vaccine. 1999 Mar 26;17(13-14):1681-9
references.pmid: 10194823
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2903-8
references.pmid: 17299053
references.citation: Antimicrob Agents Chemother. 2011 Feb;55(2):459-72
references.pmid: 21078929
references.citation: J Virol. 2002 May;76(10):5220-32
references.pmid: 11967336
references.citation: Biochim Biophys Acta. 2005 May 25;1723(1-3):270-81
references.pmid: 15823507
references.citation: Vaccine. 2006 Mar 6;24(10):1515-22
references.pmid: 16288820
references.citation: Adv Drug Deliv Rev. 2003 Nov 14;55(11):1497-513
references.pmid: 14597143
references.citation: Fitoterapia. 2012 Mar;83(2):348-55
references.pmid: 22155187
references.citation: Mutat Res. 1999 Jan;436(1):69-97
references.pmid: 9878691
references.citation: J Virol. 2003 Sep;77(17):9533-41
references.pmid: 12915567
references.citation: Food Chem Toxicol. 2013 Feb;52:207-15
references.pmid: 23182741
references.citation: J Appl Microbiol. 2003;95(3):412-27
references.pmid: 12911688
references.citation: Virology. 2006 Jan 5;344(1):17-24
references.pmid: 16364731
references.citation: Mol Nutr Food Res. 2011 Feb;55(2):198-208
references.pmid: 20669245
references.citation: Virology. 2008 Jul 5;376(2):279-89
references.pmid: 18452963
references.citation: J Virol. 1998 Mar;72(3):2010-21
references.pmid: 9499055
references.citation: Clin Exp Dermatol. 2007 Nov;32(6):625-30
references.pmid: 17953630
references.citation: Antimicrob Agents Chemother. 2013 Aug;57(8):3806-14
references.pmid: 23716050
references.citation: Antimicrob Agents Chemother. 2011 Dec;55(12):5646-53
references.pmid: 21947401
references.citation: Mol Nutr Food Res. 2007 Jan;51(1):116-34
references.pmid: 17195249
references.citation: Food Funct. 2013 Jan;4(1):10-8
references.pmid: 23037977
references.citation: J Agric Food Chem. 2005 Jul 27;53(15):6146-50
references.pmid: 16029009
references.citation: Antiviral Res. 2002 Jul;55(1):53-62
references.pmid: 12076751