Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite
Laura-Oana Albulescu, Melissa Hale, Stuart Ainsworth, Jaffer Alsolaiss, Edouard Crittenden, Juan J. Calvete, Chloe A. Evans, Mark C. Wilkinson, Robert A. Harrison, Jeroen Kool, Nicholas R. Casewell
Abstract
-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a "challenge and treat" model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.