A Cyclic Peptide Based on Pheasant Cathelicidin Inhibits Influenza A H1N1 Virus Infection

Area of Science:

• Virology
• Immunology
• Medicinal Chemistry

Background:

• Influenza viruses cause significant public health threats, necessitating new antiviral treatments due to constant viral mutation.
• Antimicrobial peptides (AMPs) are emerging as promising candidates for developing novel anti-influenza therapeutics.
• Pheasant cathelicidin serves as a basis for designing new molecules with potential antiviral properties.

Purpose of the Study:

• To design and evaluate novel peptides based on pheasant cathelicidin for anti-influenza activity against the H1N1 virus.
• To investigate the antiviral mechanisms of action for the designed peptides.
• To assess the therapeutic potential of these peptides in a preclinical model.

Main Methods:

• Design of peptides based on pheasant cathelicidin structure.
• In vitro testing of peptide antiviral activity against H1N1 virus, including IC50 determination.
• Analysis of peptide-induced immune responses, including type I interferons and interferon-stimulated genes.
• In vivo efficacy study using a mouse model of H1N1 infection.

Main Results:

• Two designed peptides, Pc-4 and Pc-5, demonstrated significant inhibition of H1N1 virus replication with low IC50 values (8.14 ± 3.94 µM and 2.47 ± 1.95 µM, respectively).
• The cyclic peptide Pc-5 was shown to induce type I interferons and upregulate interferon-induced gene expression.
• In a mouse model, Pc-5 effectively suppressed H1N1 virus infection.

Conclusions:

• A strategy for designing cyclic peptides with therapeutic potential against influenza A virus was established.
• Pc-4 and Pc-5 represent novel peptide-based therapeutic candidates for treating H1N1 influenza infections.
• The findings highlight the potential of cathelicidin-derived peptides in combating influenza virus threats.