Distinct pathophysiological mechanisms of Heterometrus laoticus and Lychas mucronatus scorpion venoms on cardiovascular and renal functions

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  Distinct pathophysiological mechanisms of Heterometrus laoticus and Lychas mucronatus scorpion venoms on cardiovascular and renal functions Abstract Background:    Heterometrus laoticus and Lychas mucronatus are widely distributed in Southeast Asia, yet their pathophysiological effects of both venoms remain poorly characterized due to low human fatality rates. This study compared their venom compositions and acute cardiovascular and renal effects. Methods:   Anesthetized male New Zealand White rabbits were monitored for blood pressure (BP), heart rate (HR), and renal clearance following intravenous administration of crude venom (0.5 mg/kg). Venom components were identified via LC-MS/MS, and hematological/biochemical parameters were assessed. Results:    H. laoticus venom induced a rapid, transient hypotension ( p < 0.05), followed by a mild, prolonged hypotensive phase (up to 120 min). Conversely, L. mucronatus venom elicited a biphasic response: ...

Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites

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Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites

Abstract

Each year, snakebite envenoming claims thousands of lives and causes severe injury to victims across sub-Saharan Africa, many of whom depend on antivenoms derived from animal plasma as their sole treatment option1. Traditional antivenoms are expensive, can cause adverse immunological reactions, offer limited efficacy against local tissue damage and are often ineffective against all medically relevant snake species2. There is thus an urgent unmet medical need for innovation in snakebite envenoming therapy. However, developing broad-spectrum treatments is highly challenging owing to the vast diversity of venomous snakes and the complex and variable composition of their venoms3. Here we addressed this challenge by immunizing an alpaca and a llama with the venoms of 18 different snakes, including mambas, cobras and a rinkhals, constructing phage display libraries, and identifying high-affinity broadly neutralizing nanobodies. We combined eight of these nanobodies into a defined oligoclonal mixture, resulting in an experimental polyvalent recombinant antivenom that was capable of neutralizing seven toxin families or subfamilies. This antivenom effectively prevented venom-induced lethality in vivo across 17 African elapid snake species and markedly reduced venom-induced dermonecrosis for all tested cytotoxic venoms. The recombinant antivenom performed better than a currently used plasma-derived antivenom and therefore shows considerable promise for comprehensive, continent-wide protection against snakebites by all medically relevant African elapids.

Ahmadi, S., Burlet, N. J., Kerwin, S., Cardoso, I. A., Marriott, A. E., Edge, R. J., Crittenden, E., L., M., Nguyen, G. T., Wouters, Y., Kalogeropoulos, K., Thumtecho, S., Ebersole, T. W., Dahl, C. H., U., E., Jansen, T., Boddum, K., Manousaki, E., Ward, A. B., . . . Laustsen, A. H. (2025). Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites. Nature, 1-10. https://doi.org/10.1038/s41586-025-09661-0