Venom variation and the future of antivenom design: Integrating population venomics, evolutionary toxinology, and precision therapeutics

Snakebite envenoming remains a neglected tropical disease that disproportionately affects rural populations in the tropical regions, where access to timely and effective treatment is often limited. Conventional antivenoms, produced by immunizing animals with pooled venoms, have demonstrated clinical benefit but may show variable performance against the complex and geographically heterogeneous composition of snake venoms. Advances in proteomics, transcriptomics, and genomics have revealed substantial intra- and interspecies venom variation with potential implications for antivenom design and evaluation. This review synthesizes current knowledge on the molecular, ecological, and evolutionary drivers of venom diversity and discusses how these insights may inform the development of more regionally informed and evidence-based therapeutic strategies. Particular attention is given to toxin-resolved antivenomics, monoclonal antibody research, recombinant platforms, and emerging computational tools for antigen prioritization. The potential role of rapid diagnostics and immunoinformatics in supporting clinical decision-making is also considered. Overall, the review highlights how population-level venom data and translational research may contribute to incremental improvements in antivenom design, while acknowledging the regulatory, economic, and implementation challenges involved. • Snake venoms vary across species and populations, influencing antivenom efficacy. • Population venomics and antivenomics enable toxin-informed antivenom design. • Recombinant antibodies and toxin-focused immunogens expand design options. • Diagnostics, artificial intelligence (AI), and regulation shape future precision antivenom strategies.