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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Virology

A Hedgehog Cathelicidin-Derived Peptide Exhibits Antiviral Activity Against Herpes Simplex Virus Type 1 Infection

Provisionally accepted
Enjie DengEnjie Deng1Yaping PeiYaping Pei1Kun YuanKun Yuan1Juan YangJuan Yang2Suncheng-ai CaoSuncheng-ai Cao1Xinyan YangXinyan Yang1Guilan LiGuilan Li1Libin LiangLibin Liang1Lin JinLin Jin1*Tengyu ZhuTengyu Zhu1*
  • 1Shanxi Agricultural University, Taiyuan, China
  • 2First Affiliated Hospital of Kunming Medical University, Kunming, China

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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.

Keywords: Antiviral activity, CathEE-2a, Drug candidate, hedgehog cathelicidin, HSV-1, Type I Interferons

Received: 17 Dec 2025; Accepted: 04 Feb 2026.

Copyright: © 2026 Deng, Pei, Yuan, Yang, Cao, Yang, Li, Liang, Jin and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Lin Jin
Tengyu Zhu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material