Danger in the reef proteome , toxicity , and neutralization of the venom of the olive sea snake ,

41 Four specimens of the olive sea snake, Aipysurus laevis, were collected off the 42 coast of Western Australia, and the venom proteome was characterized and 43 quantitatively estimated by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses. A. 44 laevis venom is remarkably simple and consists of phospholipases A2 (71.2%), three45 finger toxins (3FTx; 25.3%), cysteine-rich secretory proteins (CRISP; 2.5%), and traces 46 of a complement control module protein (CCM; 0.2%). Using a Toxicity Score, the 47 most lethal components were determined to be short neurotoxins. Whole venom had an 48 intravenous LD50 of 0.07 mg/kg in mice and showed a high phospholipase A2 activity, 49 but no proteinase activity in vitro. Preclinical assessment of neutralization and ELISA 50 immunoprofiling showed that BioCSL Sea Snake Antivenom was effective in cross51 neutralizing A. laevis venom with an ED50 of 821 μg venom per mL antivenom, with a 52 binding preference towards short neurotoxins, due to the high degree of conservation 53 between short neurotoxins from A. laevis and Enhydrina schistosa venom. Our results 54 point towards the possibility of developing recombinant antibodies or synthetic 55 inhibitors against A. laevis venom due to its simplicity. 56