Helical peptides derived from lactoferrin bind hepatitis C virus envelope protein E2.

Area of Science:

• Virology
• Biochemistry
• Drug Discovery

Background:

• Hepatitis C virus (HCV) causes chronic liver disease, cirrhosis, and liver cancer, affecting over 170 million people globally.
• HCV entry into hepatocytes is mediated by the binding of its envelope 2 glycoprotein (E2) to cell-surface receptors.
• Human lactoferrin-derived peptides have demonstrated the ability to inhibit HCV entry by binding to the E2 protein.

Purpose of the Study:

• To synthesize and evaluate biotin-linked alpha-peptides derived from human lactoferrin for their binding activity to the Hepatitis C virus E2 protein.
• To identify novel peptide inhibitors of Hepatitis C virus entry.

Main Methods:

• Expression and purification of Hepatitis C virus E2 protein (genotype 1b) using affinity chromatography.
• Synthesis of biotin-linked alpha-peptides from a 33-residue human lactoferrin peptide.
• Development of a biotin-streptavidin based binding assay to determine peptide-E2 binding affinity.
• Circular dichroism spectroscopy to assess peptide helicity.

Main Results:

• Two synthesized peptides exhibited specific binding to the E2 protein with affinities in the submicromolar to low micromolar range (K(d) = 0.569 and 28.8 microM).
• These high-affinity binding peptides also displayed the highest helical content in solution.
• A correlation between increased helicity and enhanced binding affinity was observed.

Conclusions:

• Novel human lactoferrin-derived peptides effectively bind to the Hepatitis C virus E2 protein.
• These peptides represent promising lead compounds for the development of new Hepatitis C virus entry inhibitors.
• The findings suggest a potential therapeutic strategy to prevent Hepatitis C virus infection by blocking viral entry.