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Tackling the Threat of Snakebite Envenoming

A look at the dangers of snakebites and the need for better treatments.

Keirah E. Bartlett, Adam Westhorpe, Mark C. Wilkinson, Nicholas R. Casewell

― 5 min read


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Snakebite envenoming is a big problem, especially in rural areas of countries in sub-Saharan Africa, South Asia, Southeast Asia, and Latin America. Each year, it causes up to 138,000 deaths and leads to around 400,000 disabilities. The World Health Organization (WHO) has recognized snakebite as a neglected tropical disease and aims to cut the number of deaths and disabilities in half by the year 2030. The main treatment available is antivenom, which can save lives but comes with issues like cost and effectiveness.

Understanding Snake Venoms

Snake venoms are complex mixtures of proteins that can cause various harmful effects. Some venoms create serious issues throughout the body, while others mainly cause severe damage at the bite site. In many cases, the localized damage can result in the loss of limbs or require surgical action. In Africa, thousands of people end up needing limb amputations due to snakebites every year.

The venom from certain snakes like the puff adder and saw-scaled viper is known for causing significant local damage. In Nigeria, a particular type of saw-scaled viper contributes greatly to severe cases of envenoming. The puff adder's venom also causes widespread issues in many regions.

What’s Inside Snake Venom?

The Toxins in snake venom come from different families of proteins. Scientists have found that certain proteins like snake venom metalloproteinases (SVMPs) and phospholipases A2 (PLA2) are common in the venoms of problematic snakes. Each type of venom differs in its makeup.

For example, in Nigeria, the puff adder's venom has a lot of C-type lectin-like proteins, while the saw-scaled viper's venom contains more SVMPs. Even different regions might have snakes with different venom properties.

The Damage Caused by Venoms

When snakes bite, the venom can lead to life-threatening conditions or severe local damage. This can include bleeding, muscle death, and other serious problems. The types of toxins in the venom can cause various effects on the body, with some targeting blood and others affecting tissue directly.

The mystery remains about which specific venom components cause the most harm. Some historical studies have hinted that different types of toxins contribute to the overall harmful effects, but many details are still unclear.

Cell Damage from Venom

In experiments on human skin cells, researchers found that both the saw-scaled viper and the puff adder venoms can cause significant cell damage. The saw-scaled viper's venom has been shown to be slightly more harmful than that of the puff adder in these tests.

When scientists examined the individual components of the venoms, it became clear that SVMPs were primarily to blame for the cell damage. These proteins, especially the PIII subtype from the saw-scaled viper, were the main culprits.

Break it Down: How Researchers Study Venoms

To investigate further, researchers separated the venoms into different parts and tested which parts caused cell damage. They found that certain fractions of the saw-scaled viper's venom were particularly toxic, while other parts of the puff adder venom also showed harmful effects. When the scientists used a special agent to inhibit SVMPs, they found that it significantly reduced the damage caused by both venoms.

The Role of EDTA

EDTA is a compound that can inhibit proteases, which are enzymes that break down proteins. By using EDTA in the tests, researchers could observe a major reduction in the harmful effects of the venoms. This finding suggests that SVMPs play a key role in the cytotoxic effects of the venoms.

By finding ways to effectively block these toxins, researchers are hopeful about developing better treatments for snakebite victims.

Variations Among Snake Venoms

Different species of snakes can have varied venom, even within the same species in different regions. Researchers found that the puff adder's venom from Tanzania was much more harmful than that from Nigeria when tested on human skin cells.

You could say that snakes from Nigeria and Tanzania have their own brewing methods for their venom, and it turns out the Tanzanian version packs a bigger punch!

Testing and Research Methods

The researchers used a combination of techniques to break down the venoms and test their effects on cells. By combining size separation with specific assays-like the MTT assay that measures cell viability-the scientists could learn a lot about which components of the venom were doing the damage.

Moving Forward: New Treatments

Given the fact that antivenom is not always effective or affordable, there is a push to create new treatments. These could include monoclonal antibodies or small molecule inhibitors, which would specifically target the harmful toxins in snake venom.

Understanding the specific components causing issues allows researchers to develop new therapies that may render current antivenoms obsolete.

What’s Next?

This research opens the door for new advancements in medicine to deal with snakebites. While current treatments are limited, the studies point towards potentially effective alternatives that could mitigate the serious dangers posed by snakebites in the future.

We can only hope that these advancements come quickly, so fewer people will have to worry about their next encounter with a snake-especially in rural areas where these incidents are far too common.

Conclusion

Snakebite envenoming is a significant global health issue, especially in tropical regions. The complexities of snake venoms and their effects on the human body highlight the necessity for continued research to improve treatment options.

With a bit of humor, one might say that snakes have a flair for dramatic entrances-especially when their venom is involved. By unraveling the mysteries of these venoms, scientists are moving closer to finding effective solutions that could save lives and limbs alike. So, let’s keep our fingers crossed that the next cure for snakebite woes is right around the corner!

Original Source

Title: Snake venom metalloproteinases are predominantly responsible for the cytotoxic effects of certain African viper venoms

Abstract: AbstractSnakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The puff adder (Bitis arietans) and saw-scaled viper (Echis romani) have cytotoxic venoms that cause permanent injury via tissue-destructive dermonecrosis around the bite site. Identification of cytotoxic toxins within these venoms will allow development of targeted treatments, such as small molecule inhibitors or monoclonal antibodies to prevent snakebite morbidity. Venoms from both species were fractionated using gel filtration chromatography, and a combination of cell-based cytotoxicity approaches, SDS-PAGE gel electrophoresis, and enzymatic assays were applied to identify venom cytotoxins in the resulting fractions. Our results indicated that snake venom metalloproteinase (SVMP) toxins are predominately responsible for causing cytotoxic effects across both venoms, but that the PII subclass of SVMPs are likely the main driver of cytotoxicity following envenoming by B. arietans, whilst the structurally distinct PIII subclass of SVMPs are responsible for conveying this effect in E. romani venom. Identification of distinct SVMPs as the primary cytotoxicity-causing toxins in these two African viper venoms will facilitate the future design and development of novel therapeutics targeting these medically important venoms, which in turn could help to mitigate the severe life and limb threatening consequences of tropical snakebite. Key ContributionSVMP toxins were identified as the primary cytotoxicity-causing toxins in the venoms of the puff adder (Bitis arietans) and saw-scaled viper (Echis romani); PII and PIII SVMPs, respectively. This cytotoxicity can be prevented using the metalloproteinase-inhibiting chelator EDTA, suggesting targeted drugs/antibodies may be a viable option for future treatment.

Authors: Keirah E. Bartlett, Adam Westhorpe, Mark C. Wilkinson, Nicholas R. Casewell

Last Update: 2024-12-07 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.04.626778

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.04.626778.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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