Toxinology of Venoms from Five Australian lesser known Elapid Snakes

Abstract

Research into Australian elapid venoms has mainly focused on the seven genera of greatest clinical significance: Acanthophis, Hoplocephalus, Notechis, Oxyuranus, Pseudechis, Pseudonaja and Tropidechis. However, even small species represent a potential for causing severe clinical envenoming. Further, due to taxonomic distinctiveness, these species are a potential source of novel toxins for use in drug design and development. This is the first study to characterise the venoms of Cryptophis boschmai, Denisonia devisi, Echiopsis curta, Hemiaspis signata and Vermicella annulata. MALDI analysis of each venom, over the range of 4‐40 kDa, indicated components in the weight range for 3 finger toxins (6‐8 kDa) and PLA₂ (12‐14 kDA). Interestingly, C. boschmai venom was the only venom which contained components >25kDa. All venoms (10 μg/ml) demonstrated in vitro neurotoxicity in the chick biventer cervicis nerve‐muscle preparation, with a relative rank order of: H. signata ≥ D. devisi ≥ V. annulata = E. curta > C. boschmai. CSL polyvalent antivenom neutralised the inhibitory effects of C. boschmai venom but only delayed the inhibitory effect of the other venoms. All venoms displayed PLA₂ activity but over a wide range (i.e. 1‐621 μmol/min/mg). The venoms of C. boschmai (60 μg/kg, i.v.), D. devisi (60 μg/kg, i.v.) and H. signata (60 μg/kg, i.v.) produced hypotensive effects in vivo in an anaesthetised rat preparation. H. signata displayed moderate pro‐coagulant activity while the other venoms were weakly pro‐coagulant. This study demonstrated that these understudied Australian elapids have varying pharmacological activity, with notable in vitro neurotoxicity for four of the venoms, and may produce mild to moderate effects following systemic envenoming.