Drug discovery: Drug combination protects against multiple snake venoms in mice

A combination of two small molecule toxin inhibitors is shown to protect mice against the venoms from multiple species of vipers, reports a study in Nature Communications. The findings suggest that combinations of toxin inhibitors could lead to the development of broad-spectrum therapies to treat snakebites.

Snakebites result in approximately 138,000 deaths a year in the rural communities of sub-Saharan Africa, South and Southeast Asia, and Central and South America. Differences in the composition of snake venoms mean that antibody-based antivenoms tend to only be effective against bites from specific snake species.

Nicholas Casewell and colleagues explored the potential of using combinations of small molecule toxin inhibitors as broad-spectrum therapeutics against snake venom. In laboratory experiments, the authors found that a number of molecules that had undergone phase-2 clinical trials were capable of neutralizing viper venoms by inhibiting different families of toxins. In experiments involving mice, a single dose of a combination of two inhibitors (marimastat and varespladib) was administered 15 minutes after viper venom, and the animals were monitored for 24 hours afterwards. The authors found that these molecules were capable of preventing the death of the mice, and were shown to be effective against the venoms from a range of vipers from Africa, South Asia and Central America.

The authors conclude that their data provides evidence that combinations of small molecule toxin inhibitors can neutralize medically important snake venoms. Further preclinical studies are required, but they suggest that these therapies could, in the future, provide prehospital treatments for snakebites.