This study designed and optimized Asian elephant-derived cathelicidin peptides, discovering that EM-1 demonstrates significant anti-HSV-1 activity both in vitro and in vivo with low toxicity and immunomodulatory properties, providing a novel candidate molecule for antiviral drug development.
Literature Overview
The article 'Elephant Cathelicidin-Derived Peptides Inhibit Herpes Simplex Virus 1 Infection', published in the journal Antibiotics, reviews and summarizes the anti-HSV-1 activity and mechanism of Asian elephant cathelicidin-derived peptides. The research team identified low-toxicity peptides EM-1 and EM-2 through structural optimization, validated their antiviral effects in vitro and in mouse models, and revealed their potential mechanism involving upregulation of IFN-γ and downstream genes ISG15 and MX1 to enhance host antiviral immunity.
Background Knowledge
Herpes Simplex Virus Type 1 (HSV-1) is a globally prevalent DNA virus causing oral herpes, viral encephalitis, and infectious blindness. Although acyclovir (ACV) is the primary treatment, its drug resistance is increasing, and it cannot effectively target latent viruses. Antimicrobial peptides (AMPs), as natural immune effector molecules, exhibit broad-spectrum antiviral activity without inducing resistance but face challenges in clinical translation due to poor stability and low bioavailability. Recently, cathelicidin-type AMPs have gained attention for their structural stability and immunomodulatory functions. This study optimized anti-HSV-1 peptides based on Asian elephant cathelicidin, systematically evaluating their antiviral activity and mechanisms through in vitro experiments and mouse models to provide theoretical support for developing novel HSV-1 therapeutic strategies.
Research Methods and Experiments
The research team obtained the mature cathelicidin peptide EM from the Asian elephant (Elephas maximus) in the NCBI database and designed four derivatives (EM-1 to EM-4) through sequence optimization. Structural features were predicted using HeliQuest and I-TASSER to identify low-toxicity, high-antiviral activity candidates. In vitro, HSV-1-infected U251 cells were treated with EM-1 or EM-2, followed by qPCR analysis of viral gene UL30 copy numbers and CCK-8 assays for cytotoxicity evaluation. RT-qPCR analyzed expression changes in IFN-γ, ISG15, and MX1. In vivo, a footpad infection model was established in C57BL/6J mice using HSV-1, followed by intraperitoneal injection of EM-1 or ACV. Viral loads in brain, lung, and heart tissues were measured, and H&E staining assessed histopathological changes.
Key Conclusions and Perspectives
Research Significance and Prospects
EM-1, as a novel cathelicidin-derived peptide, combines direct anti-HSV-1 activity with immune-enhancing properties, offering a promising candidate for broad-spectrum antiviral therapy. Future studies should investigate its mechanisms in additional cell models, explore synergistic effects with existing antivirals, and evaluate its broad antiviral potential in other viral infection models.
Conclusion
This study successfully designed and optimized EM-1, a novel anti-HSV-1 peptide derived from Asian elephant cathelicidin, demonstrating its antiviral and immunomodulatory functions in vitro and in vivo. EM-1 enhances host antiviral defenses by upregulating IFN-γ and downstream ISGs, effectively suppressing HSV-1 replication in mouse footpad infection models, particularly in brain tissue where it outperforms traditional drug acyclovir. The research reveals cathelicidin peptides' therapeutic potential for antiviral treatments and provides structural optimization strategies for developing multi-target antiviral drugs. Future investigations should focus on pharmacokinetics, tissue distribution, and long-term toxicity to advance clinical translation.
