Integrative venomics of the coral snake Micrurus elegans: composition, toxicity, and neutralization by antivenom

The venoms of Mexican coral snakes remain poorly characterized despite the clinical importance of neurotoxic envenomation. In this study, we present the first comprehensive analysis of Micrurus elegans venom, combining transcriptomic, proteomic, biochemical, and functional methods, including testing the neutralization capacity of the currently available Mexican coral snake antivenom (Coralmyn®). De novo assembly of the venom gland transcriptome identified 63 toxin-encoding transcripts, with three-finger toxins (3FTx) as the predominant family. Shotgun proteomics confirmed this pattern, with 3FTx making up over 60% of the venom proteome, followed by phospholipases A₂ (PLA₂). Functional assays showed that low-molecular-weight fractions, consistent with α-neurotoxins, were mainly responsible for lethality in mice, while PLA₂-rich fractions were non-lethal and exhibited low enzymatic activity. Screening combined showed lethality when a 3FTx-rich fraction and a PLA₂-rich fraction were administered together, and, based on sequence similarity to multimeric toxins previously described in other Micrurus species, suggest the possible presence of a Brownitoxin-like interaction. Neutralization assays showed reduced neutralizing capacity of Coralmyn® under the conditions tested, with one batch failing to neutralize a 3LD₅₀ challenge, and another requiring high doses of antivenom. ELISA results showed reduced recognition of the most lethal α-neurotoxin compared to PLA₂ components. These findings identify M. elegans as a species whose venom is dominated by α-neurotoxins and highlight the importance of aligning antivenom immunization strategies with toxin composition to improve treatment outcomes.