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


CONCLUSIONS
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.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: tanngethong@yahoo.com.sg.
Nget Hong
NH
Tan
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Shin Yee
SY
Fung
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Kae Yi
KY
Tan
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Michelle Khai Khun
MK
Yap
Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
Christeine Ariaranee
CA
Gnanathasan
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur Malaysia. Electronic address: tanchoohock@gmail.com.
Choo Hock
CH
Tan
D053878:Hemolytic Agents / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods; D009498:Neurotoxins / Q000737:chemistry*; D010449:Peptide Mapping / Q000379:methods; D054467:Phospholipases A2 / Q000737:chemistry*; D020543:Proteome / Q000737:chemistry*; D040901:Proteomics; D014757:Viper Venoms / Q000737:chemistry*
D053878:Hemolytic Agents; D009498:Neurotoxins; D020543:Proteome; D014757:Viper Venoms; D054467:Phospholipases A2
Daboia russelii; Presynaptic neurotoxicity; Snaclecs; Sri Lankan Russell's viper; Venom proteome; Venomics