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Inhibition of Herpes Simplex Virus-1 by the Modified Green Tea Polyphenol EGCG-Stearate

Herpes Simplex Virus-1 (HSV-1) is a member of the family Herpesviridae, and subfamily Alphaherpesvirinae. Herpesviruses are double-stranded, and enveloped DNA viruses that cause a wide range of diseases in humans and other animals. HSV-1 undergoes both lytic and lysogenic infection cycles. HSV-1’s infection cycle begins with a rapid lytic infection of epithelial cells (typically oral) in vivo and in susceptible cultured cells in vitro. HSV-1 is also neurotropic and infection proceeds into nearby neurons via retrograde axonal transport, ultimately resulting in life-long latency in host sensory neurons. Since, the virus undergoes lysogenic infection, the immune system of an individual could never get rid of the virus completely. Therefore, recurrent viral infections are always a threat for HSV infected individuals.

Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, is the primary catechin obtained from leaves of the Camellia sinensis plant. EGCG has been previously demonstrated to have antiviral properties against several viruses including HIV, hepatitis B, hepatitis C, influenza, adenovirus, and Zika. EGCG has been shown to inhibit HSV-1 in Vero cells prior to virus adsorption. However, EGCG is chemically unstable and sensitive to biological transformation reactions. The structure of EGCG was modified by esterification to produce a lipophilized EGCG-acyl ester derivative containing stearic acid, also termed EGCG-Stearate (EGCG-S). Due to the enhanced solubility, EGCG-S is a more potent form that can be used in formulations to be applied in medicine.

The goal of this study is to assess the potential of EGCG-S to provide a novel therapeutic treatment to inhibit HSV-1 infections. In this study, 25 μM, 50 μM, 75 μM, and 100 μM of EGCG and EGCG-S were used to carry out cytotoxicity, cell viability and cell proliferation assays to determine the maximum non-cytotoxic concentrations on cultured A549 cells.

The results suggested that 75 μM of EGCG and EGCG-S is the appropriate concentration to further study the effect on the infection of HSV-1 in A549 cells. Infectivity, antiviral, and inverted microscopy assays were performed to study the effects of EGCG and EGCG-S on HSV-1 infection. An antiviral assay was performed using luminescence and it indicated that EGCG-S treated HSV-1 showed up to 90% inhibition. Confocal microscopy images further supported the inhibitory effects of 75 μM EGCG-S on HSV-1 infection in A549 cells.

In conclusion, EGCG-S, a more stable and lipid soluble derivative of EGCG, does not affect cellular morphology; is not cytotoxic; and can inhibit the infection of HSV-1 in cultured cells. EGCG-S shows promise for use as a topical therapeutic treatment to limit the spread of HSV-1 infections.  

Article by Shivani N. Patel, et al, from Montclair State University, Montclair, NJ, USA.

Full access: http://t.cn/EbXqJZt
Image by Roberto Maxwell, from Flickr-cc.

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