# A hedgehog cathelicidin-derived peptide exhibits antiviral activity against herpes simplex virus type 1 infection

## TL;DR

A peptide derived from hedgehog skin shows strong antiviral effects against herpes simplex virus type 1, reducing viral load and brain damage in mice.

## Contribution

The study identifies CathEE-2a, a hedgehog cathelicidin-derived peptide, as a novel immunomodulatory antiviral agent with therapeutic potential against HSV-1.

## Key findings

- CathEE-2a significantly reduced HSV-1 brain viral loads in a mouse model.
- CathEE-2a attenuated HSV-1-induced brain damage as shown by histopathological analyses.
- CathEE-2a suppressed HSV-1 infection by upregulating type I interferons and antiviral genes.

## Abstract

Herpes simplex virus type 1 (HSV-1) is a widespread infectious virus that poses a substantial public health burden. With no specific curative therapy available and current antivirals providing only symptomatic relief, the development of new effective antiviral agents remains imperative. Antimicrobial peptides, particularly cathelicidins, are key immune effector molecules with antiviral and immunomodulatory properties. In this study, we found that European hedgehog skin extract (HSE) exhibited potent anti-HSV-1 activity, prompting us to investigate the contribution of the cathelicidin peptide CathEE. Based on this observation, three CathEE-derived antiviral peptides (CathEE-1, CathEE-2, and CathEE-3) were designed and further optimized to yield CathEE-2a and CathEE-2b. Notably, CathEE-2a displayed pronounced antiviral activity in vitro and significantly reduced brain viral loads in an HSV-1 mouse infection model. Histopathological analyses further revealed that CathEE-2a attenuated HSV-1-induced brain damage. Mechanistically, CathEE-2a suppressed HSV-1 infection by upregulating type I interferons and downstream antiviral genes. Collectively, these findings identify CathEE-2a as an immunomodulatory antiviral peptide and a promising lead candidate for the development of novel therapeutics against HSV-1 infection, highlighting the therapeutic potential of hedgehog-derived antimicrobial peptides in antiviral drug discovery.