Date of Award

1-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

Sandra D. Adams

Committee Member

Nina Goodey

Committee Member

John Siekierka

Subject(s)

Herpes simplex virus, Epigallocatechin gallate, Green tea--Therapeutic use

Abstract

Herpes simplex virus type 1 (HSV-1) is the causative agent of oral herpes, and is able to establish lifelong latent infection along with painful, recurring symptoms. Epigallocatechin-3- gallate (EGCG) is the most abundant polyphenol derived from green tea (Camellia sinensis), whose anti-inflammatory, antioxidant, anti-cancer, and antiviral properties have been widely studied. Although EGCG is not chemically stable and has poor hydrophobicity, lipophilic derivatives of EGCG have shown increased stability as well as increased antiviral efficacy against HSV. Previous studies have demonstrated that EGCG stearate (EGCG-S), a derivative of EGCG esterified at the 4’ position with stearic acid, is able to inhibit HSV-1 infection in cell culture. However, the mechanism of action of EGCG-S has not been fully determined. Since EGCG has been shown to inhibit HSV infection by interrupting viral attachment to cell membrane receptors, it is hypothesized that EGCG-S inhibits HSV-1 infection by blocking virion binding in a similar fashion. Through luminescence-based assays, this project investigates the anti-HSV-1 mechanism of EGCG-S in human epithelial cells, with specific focus on inhibition of HSV-1 binding. Antiviral effect was found to occur in a dose-dependent manner, with 85.87 ± 0.07% inhibition exerted by 100 μM EGCG-S and 29.51 ± 0.13% inhibition by 75 μM. Upon assessment of inhibition of HSV-1 penetration, 75 and 50 μM EGCG-S caused 44.9 ± 0.2% and 40.5 ± 0.2% inhibition respectively, whereas 100 μM EGCG-S showed 63.23 ± 0.13% inhibition. Lastly, investigation of inhibition of HSV-1 at the initial binding step revealed that treatment with 75 μM EGCG-S resulted in 43.4 ± 0.2% inhibition, while 100 μM resulted in 97.89 ± 0.11% inhibition, virtually complete inhibition of HSV-1 binding.

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