Friday, February 23, 2024

Universal antivenom for lethal snake toxins in different snakes from Asia and Africa developed by researchers

Good news! Taking the bite out of a snake bite! 

"The discovery of a powerful antibody that neutralizes a key neurotoxin common to four deadly snake species across Asia and Africa marks an important advance in the quest for a universal antivenom against the world’s ~200 venomous snakes; up to 138,000 people die each year from snake bites."

"Researchers have discovered a potent antibody that can neutralize a key type of neurotoxin produced by four different deadly snake species from South Asia, Southeast Asia, and Africa—a step toward an antivenom that could be used on any of the 200 or so dangerous venomous snakes throughout the world.
“We are wiping out a major subclass of neurotoxins here,” ... 
For one thing, snake venoms vary a lot between species, meaning treatment depends on which species has bitten you—which is not always known. Venoms can vary even within species ..."

From the editor's summary and abstract:
"Editor’s summary
Current strategies to treat snakebite envenoming rely on polyclonal antivenom derived from animals such as horses. Although these treatments can be life-saving, they can also result in serum sickness and anaphylaxis, and they require identification of the species of snake behind the bite. To address these limitations, Khalek et al. used a synthetic human antibody library to find and optimize a monoclonal antibody that could neutralize long-chain three-finger α-neurotoxins produced by the Elapidae family of snakes, which includes cobras, kraits, and mambas. The antibody was able to confer protection against envenoming in mice and functioned by mimicking the binding between the toxins and their receptors. This antibody and the approach used to find it represent a step forward on the path toward a universal, optimized antivenom. ...
Abstract
Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming."

Universal antivenom for lethal snake toxins developed by researchers



Fig. 1. Cross-reactive anti–3FTx-L mAbs were isolated from a naive [???] library.


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