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...

Paralysis Efficiency (PD50) Scales Linearly with Lethality (LD50) in Spider Venoms

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Paralysis Efficiency (PD50) Scales Linearly with Lethality (LD50) in Spider Venoms

Abstract

Historically, venom potencies have been assessed using measures of lethality, such as the median lethal dose (LD50). However, venoms may be selected primarily for their ability to rapidly incapacitate rather than cause mortality, meaning LD50 may not capture the efficacy of venoms in an ecological and evolutionary context. To capture this context, recent studies have adapted measures that assess venoms’ ability to rapidly incapacitate, such as the median paralysis dose (PD50). However, while PD50 values are expected to provide a more proximate assessment of ecological variation in venom potency, it is unknown whether historically available LD50 values are still useful proxies of ecologically relevant potency or whether they capture independent axes of venom variation. Here, we test the relationship between LD50 and PD50 in spider venoms by experimentally estimating LD50 and PD50 for 12 species and collating additional potency data for 46 species retrieved from the literature, producing a dataset of 55 species spanning 26 families when combined. We observed a linear isometric relationship between LD50 and PD50, showing these potency measures are both strongly correlated, with an increase in paralysis efficiency associated with a similar increase in lethality. Our results suggest that due to the correlation between functional aspects of venom potency, paralysis and lethality, historically available LD50 values may be used to compare general venom potencies in spiders, provided that they are based on the same prey model.
Lyons, K., Leonard, D., McSharry, L., Martindale, M., Collier, B. L., Vitkauskaite, A., Dunbar, J. P., Dugon, M. M., & Healy, K. (2026). Paralysis Efficiency (PD50) Scales Linearly with Lethality (LD50) in Spider Venoms. Toxicon: X, 100256. https://doi.org/10.1016/j.toxcx.2026.100256