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...

Interspecific and intraspecific variability in venom composition of Naja naja and Naja kaouthia (Reptilia: Elapidae) populations from different habitats in Bangladesh

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Interspecific and intraspecific variability in venom composition of Naja naja and Naja kaouthia (Reptilia: Elapidae) populations from different habitats in Bangladesh

Abstract

The spectacled cobra (Naja naja) and monocled cobra (Naja kaouthia), widespread venomous snakes in South and Southeast Asia, occur in diverse habitats and cause neurotoxic envenoming. Despite reported venom variability of these two cobras across their range, no comparative study has been conducted from the interconnected but distinct habitats of Bangladesh. Using venomics and antivenomics, we analysed 26 individual venom samples of N. kaouthia and 17 of N. naja from Bangladesh across age groups and locations, respectively. Significant interspecific and intraspecific venom variability was observed, with geographically connected populations showing minimal divergence, while isolated populations (separated by river barriers or distinct ecosystems) exhibited pronounced compositional differences. Ontogenetic differences in venom composition between adult N. kaouthia and their juvenile offspring were detected. Commercially available Incepta polyvalent antivenom, produced against India's “Big Four” (including southern Indian N. naja), demonstrated poor efficacy against Bangladeshi cobra venoms. Collectively, our analyses demonstrate the existence of multi-dimensional variation in cobra venoms of Bangladesh that is influenced by biotic and abiotic factors. We emphasize the urgent need for region-specific antivenoms incorporating venom from ecologically distinct populations and age groups of both species across South Asia to improve snakebite treatment efficacy as well pre-clinical assessments to address biogeographic and ontogenetic venom diversity.
Chowdhury, M. A. W., Müller, J., Al Haidar, I. K., Rahman, M. M., Noman, M., Ghose, A., Sayeed, A. A., Amin, R., Sanz, L., Faiz, M. A., Kuch, U., & Calvete, J. J. (2025). Interspecific and intraspecific variability in venom composition of Naja naja and Naja kaouthia (Reptilia: Elapidae) populations from different habitats in Bangladesh. Journal of Proteomics, 105544. https://doi.org/10.1016/j.jprot.2025.105544