A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite.

ABSTRACT: Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and financial snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using murine in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination con

SUBMITTER: Albulescu LO 

PROVIDER: S-EPMC7738508 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature