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Published on: March 24, 2017
Susceptibility in vitro of Epstein-Barr Virus to myristoylated-peptide
1Department of Biological Sciences, Life Sciences Building, University of Memphis, Memphis, TN 38152-3560, USA. ddourth@memphis.edu
Abstract:
The anti-Epstein-Barr Virus (EBV) myristoylated-peptide (M.W. 916.2Da) is a natural product isolated from Heliothis virescens insect larval hemolymph (blood) that essentially has no cytotoxicity against human foreskin fibroblast cells. A (3 methyl only) version (M.W. 902.2 Da) of the structure was synthesized and tested for in vitro anti-EBV activity and cytotoxicity. The N-terminal end is lipophilic and used to get the compound across the cell membrane. The C-terminal end with its ring-shaped structures is likely used to inhibit DNA synthesis. The synthetic compound inhibited DNA synthesis/replication of EBV in Akata cells (B-lymphocyte from Burkitt's lymphoma patient) in in vitro tissue culture. A DNA hybridization assay for anti-EBV activity using the Akata B-cell and two cytotoxicity assays using human foreskin fibroblast cells were done with the synthetic peptide. Effective concentration (EC90) at 20 microM inhibited viral replication by 90%. The EBV, known as Human Herpesvirus-4 (HHV-4) of the Herpesviridae family, has been described as a cancer-promoting double-stranded DNA virus that may also be involved in autoimmune disease. There are no antiviral drugs in clinical use for diseases caused by the EBV.
Insights
A synthetic peptide effectively inhibits Epstein-Barr Virus (EBV) replication in B-lymphocytes. This natural product analog shows promise as a novel antiviral therapy against EBV, a virus linked to cancer and autoimmune diseases.
Area of Science:
- Virology
- Organic Chemistry
- Pharmacology
Background:
- Epstein-Barr Virus (EBV), also known as Human Herpesvirus-4 (HHV-4), is a double-stranded DNA virus implicated in cancer and autoimmune diseases.
- Currently, no specific antiviral drugs are clinically available for treating EBV infections.
- Natural products offer a potential source for novel antiviral agents.
Purpose of the Study:
- To synthesize and evaluate a myristoylated-peptide analog for in vitro anti-EBV activity.
- To assess the cytotoxicity of the synthetic peptide against human cells.
- To investigate the mechanism of action for inhibiting EBV DNA synthesis.
Main Methods:
- Synthesis of a modified myristoylated-peptide derived from a natural product.
- In vitro anti-EBV activity testing using a DNA hybridization assay in Akata B-cells.
- Cytotoxicity assays using human foreskin fibroblast cells.
Main Results:
- The synthetic peptide demonstrated significant inhibition of EBV DNA synthesis and replication in Akata cells.
- The effective concentration (EC90) required to inhibit viral replication by 90% was 20 microM.
- The compound exhibited minimal cytotoxicity against human foreskin fibroblast cells.
Conclusions:
- The synthetic myristoylated-peptide is a potent inhibitor of EBV replication with a favorable safety profile.
- This peptide represents a promising lead compound for developing new antiviral therapies against EBV.
- Further research is warranted to explore its therapeutic potential for EBV-associated conditions.
