Inter and intraspecific variation in Micrurus venoms from Bahia, Brazil and challenges for antivenom efficacy

Although uncommon, coral snake envenoming poses serious risks due to the neurotoxicity of Micrurus venoms. Bahia, Brazil, reports high incidence of bites, yet regional venom variation is poorly understood. This study characterized biochemical, toxicological, and immunological profiles of Micrurus ibiboboca and M. bonita venoms from adult snakes across Bahia using SDS-PAGE, shotgun proteomics and biological (lethality in mice [LD₅₀], hemorrhagic and coagulant effects, and antivenom neutralization) and enzymatic assays (PLA₂, protease, myotoxicity, edematogenic activity). Proteomics identified three venom phenotypes based on taxonomy and geographic distribution. Samples I and III were PLA₂-dominant (≈67-69%), while Sample II showed greater diversity, enriched in three-finger toxins (≈46%) and protease inhibitors (≈23%). Biological assays revealed marked variability in lethality (1.02-3.87 mg/kg), edema, and myotoxicity, with Sample I being the most toxic. Hemorrhagic and coagulant activities were absent; however, the samples demonstrated different enzymatic patterns. ELISA assays showed effective neutralization of Samples I and III by Butantan antivenom, but Sample II was poorly recognized and not neutralized, even at maximal antivenom doses. These findings demonstrate striking inter- and intraspecific venom variations in Micrurus venoms. We reiterate the urgent need for regionally informed antivenom design, as well as for the exploration of recombinant and next-generation therapies.