BIOLOGICAL SIGNIFICANCE: Laticauda colubrina (yellow-lipped sea krait) is a widely distributed, semi-aquatic venomous snake species. The venom proteome at the level of protein family is unsophisticated and consistent with its restricted prey selection. Nonetheless, the subproteomic findings revealed geographical variability of the venom for this widely distributed species. In contrast to two previous reports, the results for the Balinese L. colubrina venom showed that LNTX Neurotoxin a and Neurotoxin b were co-existent while the PLA2 lethal subtype (PLA-II) was undetected by means of LCMS/MS and by in vivo assay. This is an observable trait of L. colubrina considered divergent from specimens previously studied for the Philippines and the Solomon Islands. The stark geographical variation might be reflective of trophic adaptation following evolutionary arms race between the snake and the prey (eels) in different localities. The preferred trait would likely propagate and remain significant within the geographical population, since the strong behaviour of site fidelity in the species would have minimized gene flow between distant populations. Meanwhile, the in vivo neutralization study verified that the efficacy of the heterologous Sea Snake Antivenom (Australian product) is attributable to the cross-neutralization of SNTX and LNTX, two principal lethal toxins that made up the bulk of L. colubrina venom proteins. The findings also implied that L. colubrina, though could be evolutionarily more related to the terrestrial elapids, has evolved a much streamlined, neurotoxin- and PLA2-predominated venom arsenal, with major antigenicity shared among the true sea snakes and the Australo-Papuan elapids. The findings enrich our current understanding of the complexity of L. colubrina venom and the neutralizing spectrum of antivenom against the principal toxins from this unique elapid lineage.
METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.
CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.