A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies

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  A Paradigm Shift in Snakebite Envenoming Therapy: From Conventional Antivenoms to Rationally Designed, Broadly Neutralizing Combination Therapies Abstract For over a century, polyclonal antivenom has been the cornerstone of snakebite therapy, saving countless lives. However, the current production method, based on immunizing large animals, has inherent limitations in terms of safety, stability, and supply reliability, thereby creating a pressing need for alternative technologies. This review charts the rise of next-generation antivenoms built on recombinant antibody engineering. We systematically survey the strategies for discovering and developing these molecules, from humanized monoclonal antibodies and VHHs to computationally designed proteins. Our central thesis is that achieving broad-spectrum neutralization against complex venoms requires a shift from single-agent approaches to rationally designed, oligoclonal “cocktail” therapies (defined mixtures of a few select therapeut...

Riparian spiders make pyriform silk attachment discs that stick better when wet than those of terrestrial spiders

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Riparian spiders make pyriform silk attachment discs that stick better when wet than those of terrestrial spiders

Adhesion in wet conditions presents significant challenges due to the disruptive effects of water on interfacial bonding, spreading and curing. Many organisms have evolved adhesives that adhere strongly in damp or submerged environments. However, the pyriform silk attachment discs of the terrestrial western black widow spider lose ∼8 times their adhesive strength when wet. Here, we tested the hypothesis that riparian species of spiders have evolved attachment discs that are resistant to the adverse effects of water on adhesion. We compared adhesion of attachment discs from three terrestrial spiders from relatively dry habitats with those of three riparian spider species when discs were loaded under both dry and wet conditions. Failure modes shifted from dragline breakage in dry conditions to adhesive failure in wet conditions across all species, highlighting the impact of water on interfacial bonding. However, riparian species’ attachment discs maintained adhesive force when wet while terrestrial species experienced ∼50% reduction in peak force and work of adhesion in wet conditions. These findings suggest that riparian spider silks have evolved specializations that maintain adhesive performance of pyriform attachment discs in wet environments, offering insights into bioinspired design for water-resistant adhesives.

Bernd F. Steklis, Todd A. Blackledge; Riparian spiders make pyriform silk attachment discs that stick better when wet than those of terrestrial spiders. J Exp Biol 15 November 2025; 228 (22): jeb250902. doi: https://doi.org/10.1242/jeb.250902