Functional venomics of the Sri Lankan Russell's viper (Daboia russelii) and its toxinological correlations.

Unlabelled: The venom proteome (venomics) of the Sri Lankan Daboia russelii was elucidated using 1D SDS PAGE nano-ESI-LCMS/MS shotgun proteomics. A total of 41 different venom proteins belonging to 11 different protein families were identified. The four main protein families are phospholipase A2 (PLA2, 35.0%), snaclec (SCL, 22.4%, mainly platelet aggregation inhibitors), snake venom serine proteinase (SVSP, 16.0%, mainly Factor V activating enzyme) and snake venom metalloproteinase (SVMP, 6.9%, mainly heavy chain of Factor X activating enzyme). Other protein families that account for more than 1% of the venom protein include l-amino acid oxidase (LAAO, 5.2%), Kunitz-type serine proteinase inhibitor (KSPI, 4.6%), venom nerve growth factor (VNGF. 3.5%), 5'-nucleotidase (5'NUC, 3.0%), cysteine-rich secretory protein (CRISP, 2.0%) and phosphodiesterase (PDE, 1.3%). The venom proteome is consistent with the enzymatic and toxic activities of the venom, and it correlates with the clinical manifestations of Sri Lankan D. russelii envenomation which include hemorrhage, coagulopathy, renal failure, neuro-myotoxicity and intravascular hemolysis. The venom exhibited remarkable presypnatic neurotoxicity presumably due to the action of basic PLA2 in high abundance (35.0%). Besides, SCLs, Factor X activating enzymes (SVMPs), SVSPs, and LAAOs are potential hemotoxins (50.5%), contributing to coagulopathy and hemorrhagic syndrome in Sri Lankan D. russelii envenomation.

Significance: The study demonstrated the proteomic profile of the Sri Lankan Russell's viper venom, unraveling its complex composition of toxins and correlations with major toxic activities. The types, numbers, and relative abundances of toxins were reported. The venom content was dominated by the neurotoxic basic phospholipases A2 (>30% of total protein abundance) and several hemotoxic or coagulopathic protein families (approximately 50% in total). The proteome correlates with the functional and toxinological characterizations of the venom, and reflects the pathophysiological effects of envenomation by the Sri Lankan Russell's viper. The venom proteomics may serve to propel the understanding on pathogenesis and treatment strategy for envenomation by this viper in Sri Lanka. The enriched database contributed by the proteomic findings will be useful for comparing venom variations among Russell's vipers from different geographical areas.