If the latest antivenom study is any indication, the next breakthrough treatment for snakebites in India could come in the form of a pill. It could be more effective, affordable, and easily accessible than existing options.
In a landmark study, researchers at the Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bengaluru, tested two repurposed small-molecule inhibitors (SMIs) — varespladib and marimastat — for their ability to neutralise venom from the Russell’s viper (Daboia russelii) across different regions of India. Small-molecule inhibitors are a class of drugs that work by targeting and blocking specific molecules, primarily proteins, involved in various cellular processes. These drugs were originally developed to treat conditions such as cancer and cardiovascular disease, which also means they have already undergone human clinical trials for those uses.
Scientist and professor Kartik Sunagar at the Centre for Ecological Sciences, who led the study, told Mongabay India that unlike antivenoms, which have never undergone formal clinical trials despite being widely used in countries like India, these drugs have already passed safety and toxicity assessments. “So, we only needed to test their efficacy for snakebites,” he says.
The neutralisation experiment on one of India’s big four medically significant snakes, Russell’s viper, proved to be the clincher.
The venom of this snake is dominated by three major toxin families: SVMP, PLA₂, and SVSP, which occur in varying proportions across its geographical range. The scientists assessed the effectiveness of the two SMIs, varespladib and marimastat, in countering the toxic effects of Russell’s viper venom sourced from diverse regions. “We’ve demonstrated that a specific combination of these two drugs provides complete protection against Russell’s viper in almost every corner of India. We’ve tested them across 10 different sites in 10 different states,” Sunagar explains.
The study found that in most D. russelii populations, a single small-molecule inhibitor could neutralise lethal venom effects in preincubation tests, and in some cases, it didn’t matter which toxin family — PLA₂ or SVMP — was blocked. This is surprising, the paper notes, given the complex and variable mix of toxins typically found in snake venoms.
The study offers several advantages of the treatment. A major benefit is that these are oral drugs. “Someone bitten in a rural area can take the pill immediately, buying time or potentially avoiding antivenom altogether,” Sunagar adds. They’re also inexpensive to produce, being lab-synthesised chemicals that don’t require animals, making them a scalable alternative to conventional antivenom.
Banner image: A Russel’s viper. Image by CHANDRANUJ via Wikimedia Commons (CC BY-SA 4.0).
