A Natural Peptide from the American Cockroach Suppresses Feline Infectious Peritonitis Virus

Area of Science:

• Veterinary Virology
• Immunology
• Natural Product Chemistry

Background:

• Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease in cats with limited therapeutic options.
• Animal-derived peptides are an underexplored source of novel antiviral agents.
• Understanding FIPV pathogenesis and identifying host-directed therapies are critical.

Purpose of the Study:

• To identify and characterize antiviral peptides from natural sources targeting FIPV.
• To evaluate the anti-FIPV efficacy and mechanism of action of a Periplaneta americana-derived peptide, PI-8.
• To assess the therapeutic potential of PI-8 in a feline model of FIPV infection.

Main Methods:

• Identification and validation of PI-8 peptide binding to ISG15.
• In vitro assessment of PI-8 cytotoxicity and FIPV replication inhibition (IC50 determination).
• Analysis of gene expression (IFNA1, IFNB, ISG15, MX1) in FIPV-infected cells treated with PI-8.
• In vivo evaluation of PI-8 in FIPV-infected cats, including viral RNA quantification, tissue burden assessment, and histopathological analysis.

Main Results:

• PI-8 demonstrated low cytotoxicity (CC50 > 40 μM) and potent inhibition of FIPV replication (IC50 = 12.9 μM), acting post-entry.
• PI-8 significantly upregulated key antiviral genes, including IFNA1, IFNB, ISG15, and MX1, in infected cells.
• In vivo, PI-8 treatment reduced viral RNA levels, viral burden in multiple tissues, and alleviated pathological lesions and inflammation in FIPV-infected cats.

Conclusions:

• PI-8 is a Periplaneta americana-derived peptide with significant dual antiviral and immunomodulatory activity against FIPV.
• The anti-FIPV mechanism involves an interferon-ISG15-related antiviral response.
• PI-8 represents a promising host-directed therapeutic candidate for feline infectious peritonitis.