Artificial Antivenom Counters Various Lethal Snake Venoms

Researchers created a synthetic antibody that prevents paralysis and death from elapid venom, originating from a globally lethal snake family. This advancement brings us nearer to creating a unified antivenom that could safeguard against all types of venomous snakes.

Australia, Asia, and Africa are regions known for harboring numerous lethal snakes. Snakebite envenoming claims about 138,000 lives yearly and leaves over 400,000 with lasting disabilities. Scripps Research scientists have identified an antibody countering a key toxin from various prevalent snake species.

Breakthrough Antibody Targets Lethal Snake Toxin

Joseph Jardine, a corresponding author of the antibody-based antivenom study, highlighted, “This antibody targets a primary toxin present in various snake species, contributing to tens of thousands of annual fatalities.” He emphasized the potential significance of this discovery for individuals in low- and middle-income countries, where snakebite-related deaths and injuries are most prevalent.

Traditionally, researchers derive snakebite antivenoms from donor animals such as horses and sheep. They administer a small amount of venom to these animals, stimulating their immune systems to produce antibodies, which are subsequently extracted and refined into pharmaceutical-grade antivenom. However, aside from ethical concerns related to animal usage (including both donors and snakes), these life-saving antivenoms often provoke severe allergic reactions in recipients. Therefore, the researchers aimed to tackle these drawbacks.

Insights into Three-Finger Toxins

The researchers identified a common protein type, three-finger toxins (3FTx), in venom proteins from various elapids, which comprise around 300 primarily venomous species like mambas, cobras, brown snakes, and kraits. These 3FTx proteins, classified as a ‘superfamily,’ exhibit diverse effects, with many possessing neurotoxic properties capable of inducing complete paralysis.

Subsequently, the researchers embarked on a quest to discover an antibody capable of inhibiting this protein. They introduced the genes for 16 different 3FTx variants into mammalian cells to produce toxins in the laboratory. Using over 50 billion synthetic human antibodies, they screened for those that bound to the protein from the many-banded krait, also known as the Chinese or Taiwanese krait, which shared similarities with other 3FTx proteins.

This initial screening narrowed down the candidates to approximately 3,800 antibodies, which underwent further testing to assess their recognition of four additional 3FTx variants. Among these, thirty antibodies demonstrated recognition. Notably, one antibody, named 95Mat5, exhibited the strongest interactions across all variants.

Protection Across Multiple Venomous Species

Upon administering 95Mat5 to mice injected with toxins from the many-banded krait, Indian spitting cobra, black mamba, and king cobra, the rodents not only survived but also remained free from paralysis in all cases. Investigating the mechanism underlying the antibody’s efficacy, the researchers discovered that it mimicked the structure of the human protein typically targeted by 3FTx.

Since 95Mat5 is a synthetic (monoclonal) antibody, the production of antivenom does not necessitate donor animals or snakes.

Joseph Jardine expressed excitement, stating, “It was thrilling that we could generate a potent antibody entirely synthetically—no animals were immunized, and no snakes were used.“

While the antibody effectively counters elapid venom’s neurotoxins, the researchers emphasize that it alone does not constitute a universal antivenom. Snake venom comprises a complex mixture, necessitating the inclusion of antibodies against various major venom classes, such as different groups of 3FTx proteins in elapids and common viper toxins. This is the current focus of the researchers’ efforts.

The researchers explained, “Hence, a comprehensive universal antivenom would likely require at least four to five antibodies to adequately target the additional venom classes. The identification and development of 95Mat5 represent a crucial initial stage in the creation of a monoclonal-based universal antivenom, as it effectively counteracts one of the most diverse and toxic elements of snake venom.”

Read the original article on: New Atlas

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