There is a new Preprint available that is now undergoing peer review. You can read the draft and manuscript here: https://doi.org/10.5281/zenodo.17514183
Abstract
Across Eurasia, envenomation by the common European adder, Vipera berus, presents a significant medical challenge, primarily driven by phospholipase A₂ (PLA₂) enzymes. Traditional antivenom therapies are hampered by specificity, immunogenicity, and logistical limitations. This article, structured into distinct chapters, first establishes the biochemical challenge posed by Vipera berus venom and the central role of PLA₂. It then outlines a focused, structure-based strategy for designing synthetic peptide inhibitors that specifically target the primary toxic PLA₂ isoform in V. berus venom (UniProt: P31854). Drawing from successful precedents in inhibiting homologous viper and elapid PLA₂s, we propose a design blueprint for short peptides (5-7 amino acids) that function as high-affinity active site blockers. The proposed mechanism involves a hydrophobic peptide scaffold that anchors the inhibitor within the enzyme’s substrate-binding channel, combined with a strategically placed “warhead” residue (e.g., Tyrosine or Arginine) designed to form high-energy hydrogen bonds or salt bridges with the catalytic dyad (His48/Asp49). This approach effectively neutralises the enzyme’s toxic activity. The clinical translation of such designer peptides is made feasible by emerging on-demand manufacturing platforms, such as the RAPID system, which utilise rapid synthesis technologies to produce patient-specific therapeutics. This peptide-centric framework offers a pathway toward a new generation of precise, safe, and logistically robust antivenoms.