A combination of two molecules has been used to save animals from snakebites by venomous snakes from different continents. The combination of Marimastat and Varespladib, two already approved drugs, can save mice from snake venom, a team of British researchers announced in the journal Nature Communications.
Venomous snakebites, mostly from the Viperidae family, are a scourge for rural populations in many tropical countries. According to the WHO, they are responsible for at least 100,000 deaths per year and cause debilitating sequelae, including amputation of bitten limbs, in about 400,000 people.
Antibodies specially produced against snake venom
The antidote, antibodies made specifically against the venom of the concerned snake, is expensive, must be injected intravenously, and is often not readily available. Viper venom consists mainly of three types of enzymes, serine proteases, metalloproteases, and phospholipases, which cause bleeding and blood-clotting disorders. The researchers tested two potent inhibitors of the latter two types, marimastat and varespladib, molecules that had already been tested as potential drugs in other indications. The combined injection of the two drugs, fifteen minutes after the toxins were injected into the mice, saved the lives of all the animals.
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Substances tolerated by the human body
These results appear all the more promising because the two substances have already been shown to be well tolerated by the human body separately and at much higher doses in previous clinical studies. They have the added advantage of being equally effective when taken orally. But there is still a long way to go before they are available in all rural pharmacies in the most affected countries, whether in India, Africa, or Central America. “First, we need to study in mice how long these products have a protective effect on the blood and whether treatment should be repeated,” says Nicholas Casewell, who started the study at the Liverpool School of Tropical Medicine. Once that study is complete, the researchers will find out whether the combination of the two molecules is equally well tolerated by the human body and if it works quickly enough orally before testing it in the field.
References
Albulescu, LO., Xie, C., Ainsworth, S. et al. A therapeutic combination of two small-molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. Nat Commun 11, 6094 (2020). https://doi.org/10.1038/s41467-020-19981-6
