Harnessing Antiviral Peptides: From Molecular Mechanisms to Clinical Translation.

Viral infections continue to pose a significant threat to global health, especially with the emergence and re-emergence of resistant viral strains. The limitations of conventional antiviral therapies, such as narrow-spectrum activity, high toxicity, and rising resistance, underscore the need for innovative treatment strategies. Antiviral peptides (AVPs) have gained attention as promising therapeutic agents due to their broad-spectrum antiviral activity, low cytotoxicity, and ability to target multiple stages of the viral life cycle. This review provides a comprehensive overview of AVPs, focusing on their classification, mechanisms of action, and clinical relevance. Both natural and synthetic AVPs are discussed, including FDA-approved agents such as enfuvirtide (HIV) and boceprevir (HCV), along with candidates currently in clinical trials. AVPs inhibit viral attachment, fusion, replication, and assembly, while also modulating host immune responses. Their applications extend beyond treatment to include prophylaxis and combination therapies, offering potential benefits in pandemic preparedness. However, challenges such as enzymatic degradation, poor bioavailability, and high production costs limit their clinical translation. Recent advances in peptide engineering, computational drug design, and nanoparticle-based delivery systems aim to overcome these barriers. AVPs represent a promising class of antiviral agents with the potential to address current therapeutic gaps and improve future outbreak response. This review highlights their growing importance in the field of antiviral therapy and outlines future directions for research and development.