Date of Award

5-2015

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Sandra D. Adams

Committee Member

Lee H. Lee

Committee Member

Quinn C. Vega

Abstract

Herpes simplex virus (HSV) is responsible for one of the most common infections within the population. The primary antiviral used against HSV infections are nucleoside analog drugs such as acyclovir and its deviates. However, in recent years the number of cases of drug resistant HSV has increased, resulting in interest for new novel treatments. Promising antiviral agents are theaflavins found within black tea derived from Camellia sinensis. These theaflavins include theaflavin (TF1), theaflavin-3-monogallate (TF2A), theaflavin-3’-monogallate (TF2B), and theaflavin-3-3’-digallate (TF3). Previous studies have supported that theaflavins from black tea, specifically TF3, inhibit the process of viral absorption. Due to this mode of action, black tea theaflavins show potential for synergistic antiviral activity when combined with drugs such as acyclovir, which inhibit viral replication. This study examined the antiviral activity of black tea extract and TF3 with acyclovir on HSV-1 and HSV-2 infections in A549 cells. Cytotoxic analysis was performed with a trypan blue, WST-1 cell proliferation, and ToxGlo assay. Data for each assay supported that concentration of 100 µM of TF3 or 100 µM BTE in combination with 50 µM of acyclovir produce no cytotoxicity in A549 cells. Antiviral activity was measured using a WST-1 based antiviral assay along with a viral ToxGlo assay. In each case theaflavins showed higher antiviral activity when combined with acyclovir, with up to 21.8% increase in viral inhibition. Moreover, the mixture showed higher antiviral activity than acyclovir alone at concentrations of 5 µM. Furthermore, isolated TF3 with acyclovir showed higher levels of viral inhibition than the combination of theaflavins with acyclovir. In conclusion, acyclovir and black tea theaflavins, TF3 in particular, have shown synergistic activity and may provide an alternative regimen, to decrease emergence of resistant strains of HSV types 1 and 2.

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