A new method to detect snake venom uses synthetic sugar molecules instead of expensive antibodies that may provide faster and cheaper diagnosis for bite victims.
Researchers at Warwick University have developed the first proof-of-concept test using sugar polymers (synthetic sugar chains), which is associated with gold nanoparticles to identify western diamond rattlesnake venom within 20 minutes. A color-changing test can help medical teams quickly determine the anti-venom to be performed in life-threatening situations.
Every five minutes, 50 people worldwide suffer from snake bites, four face permanent disability and one death. Current diagnostic methods rely heavily on antibody-based tests that are expensive, time-consuming and often inconsistent results.
Imitating the sugar target of nature
Snake venom has evolved to bind specific sugar molecules on the surface of human cells, including red blood cells and platelets. The venom of the Western Rattlesnake Rattlesnake is specifically targeted at galactose-terminal glycine-sugar chain ends with galactose-that allows toxins to destroy blood clotting and interfere with immune responses.
The team designed synthetic versions of these natural sugar receptors using sugar polymers and then attached them to gold nanoparticles. When toxin toxins bind to these synthetic sugars, the nanoparticles gather and produce visible colors that change from red to blue or purple.
“Snake venom is complex and detecting toxins at work is challenging, but it is crucial to save lives,” said Dr. Alex Baker, assistant professor and senior author of the study. “We used synthetic sugars to create an assay that mimics sugars in the body where the toxins naturally bind and makes this quick test visible.”
Key Test Performance Indicators:
- The detection limit of Western Rattlesnake Venom is about 20μg/ml
- Results can be seen within 20 minutes at room temperature
- Successfully distinguished between different snake species
- No cross-react with Indian Cobra Venom, lacks sugar-bound lectin
Beyond simple sugar recognition
The researchers created a library of gold nanoparticles functionalized by 19 different candy polymers, changing sugar type, polymer chain length and nanoparticle size. This systematic approach reveals crucial design principles that are not obvious in the initial test.
Most importantly, the study found that the length of polymer chain length greatly affects test stability and performance. The team found that longer polymer chains (52 units) successfully stabilized larger gold nanoparticles, while shorter chains (42 units) resulted in unwanted aggregation, resulting in false positive results.
A key finding overlooked in most diagnostic developments: The researchers show that lactose-terminated systems require careful optimization of polymer length and nanoparticle size to remain stable. The system with 42 unit polymer chains spontaneously aggregates 40 nanoparticles, while the same polymer works perfectly with 16 nanoparticles. Sensitivity to multiple design parameters highlights the precise engineering required for reliable diagnostic tools.
Species-specific detection capability
The sugar-based approach shows significant selectivity among different snake families. Tests of Indian Cobra Venom, which belongs to the Elapidae family, lack the lectin protein found in Vocolic venom (such as rattlesnakes), but produce no detectable signals.
“The assay could be a real game-changer for snakes,” said Mahdi Hezwani, the first author of the study. “Venom from other snake species does not interact with glycans in the body.
This specificity addresses critical medical needs. The use of the wrong antivenom may reduce the effect and may lead to serious complications, while multivalent antivenom that acts on multiple species has a higher risk of adverse side effects.
Comparative detection method
The detection limit for the new test is 20 μg/mL, which is advantageous compared to some existing methods. Previous latex agglutination tests achieved a detection limit of 167 μg/ml for Crotalus species venom. However, the most sensitive antibody-based ELISA test can detect nanomaps of content per milliliter.
Pharmacokinetic studies have shown that clinically relevant venom concentrations range from 1 to 1,000 ng/ml, up to 50 hours after venomous snake bites. Although the current sugar-based test range is higher than this range, the researchers noted that further improvements in polymer design, sugar selection and nanoparticle optimization can significantly improve sensitivity.
Better than antibody tests
Unlike antibody-based diagnosis, synthetic sugars do not require animal immunity or cell culture production. They can be chemically synthesized through precise control of structure and function, potentially reducing costs and improving consistency.
The modular design allows researchers to customize sugar recognition elements of different snake species based on known binding preferences. The same gold nanoparticle platform can accommodate a variety of sugar types to create panels that detect multiple venom types.
Storage advantages are also conducive to synthesis methods. Antibodies usually require refrigeration and have limited shelf life, while synthetic sugar polymers should prove more stable under frequent snake bites.
Future applications and development
The study, based on previous work by the Warwick team, demonstrated the versatility of sugar-based diagnostic methods using a similar GlyConanoparticle platform for COVID-19 testing.
For snake invasion, the next step involves extending testing to detect other species, especially those responsible for the global bite burden. Species in different snake families and even households may need unique sugar recognition elements based on their unique lectin spectrum.
The WHO estimates that snake venomization causes about 100,000 deaths each year, while the death to permanent disability is about three times the number of deaths, which is considered a real burden due to insufficient reporting systems. Improved diagnostic tools can help address this neglected tropical disease with more precise treatment options and better epidemiological tracking.
As Dr. Baker notes, this sugar-based assay “lays the foundation for rapid, inexpensive assays beyond antibody-based techniques.
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