Despite showing antiviral potential, a majority of antimicrobial peptides (AMPs) tested against Zika virus (ZIKV) have failed to advance toward clinical translation. A major limitation lies in their linear structure, which renders them highly susceptible to proteolytic degradation and limits cellular uptake—two properties crucial for effective antiviral action against an intracellular pathogen like ZIKV.
This poster proposes a shift in antiviral peptide design: from linear to cyclized AMPs. Cyclization enhances conformational rigidity, improves stability in physiological conditions, and facilitates endocytosis—all without compromising the native antiviral functionality. Drawing from established AMP sequences known to act on ZIKV and similar flaviviruses, we explore how head-to-tail or side-chain cyclization could restore therapeutic viability to sequences that failed in linear form.
The design-centered re-evaluation sets the stage for next-generation antiviral peptides tailored for real-world deployment. Cyclized AMPs offer a safer, more stable, and pharmacologically promising avenue for peptide-based therapeutics targeting emerging arboviruses like ZIKV.
