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Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots

Senji Laxme, RR and Khochare, S and Attarde, S and Suranse, V and Iyer, A and Casewell, NR and Whitaker, R and Martin, G and Sunagar, K (2021) Biogeographic venom variation in Russell’s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. In: PLoS Neglected Tropical Diseases, 15 (3).

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Official URL: https://doi.org/10.1371/journal.pntd.0009247


Background Snakebite in India results in over 58,000 fatalities and a vast number of morbidities annually. The majority of these clinically severe envenomings are attributed to Russell’s viper (Daboia russelii), which has a near pan-India distribution. Unfortunately, despite its medical signifi-cance, the influence of biogeography on the composition and potency of venom from dispa-rate D. russelii populations, and the repercussions of venom variation on the neutralisation efficacy of marketed Indian antivenoms, remain elusive. Methods Here, we employ an integrative approach comprising proteomic characterisation, biochemical analyses, pharmacological assessment, and venom toxicity profiling to elucidate the influence of varying ecology and environment on the pan-Indian populations of D. russelii. We then conducted in vitro venom recognition experiments and in vivo neutralisation assays to evaluate the efficacy of the commercial Indian antivenoms against the geographically dis-parate D. russelii populations. Findings We reveal significant intraspecific variation in the composition, biochemical and pharmacological activities and potencies of D. russelii venoms sourced from five distinct biogeographic zones across India. Contrary to our understanding of the consequences of venom variation on the effectiveness of snakebite therapy, commercial antivenom exhibited surpris-ingly similar neutralisation potencies against the majority of the investigated populations, with the exception of low preclinical efficacy against the semi-arid population from northern India. However, the ability of Indian antivenoms to counter the severe morbid effects of Daboia envenoming remains to be evaluated. Conclusion The concerning lack of antivenom efficacy against the north Indian population of D. russelii, as well as against two other ‘big four’ snake species in nearby locations, underscores the pressing need to develop pan-India effective antivenoms with improved efficacy in high snakebite burden locales.

Item Type: Journal Article
Publication: PLoS Neglected Tropical Diseases
Publisher: Public Library of Science
Additional Information: The copyright for this article belongs to the Authors.
Keywords: heparin; linoleic acid; oleic acid; serine proteinase inhibitor; snake venom; vasculotropin; venom; viper venom; proteome; reptilian protein; venom antiserum, activated partial thromboplastin time; animal experiment; animal model; Article; biochemical analysis; biogeographic region; biogeography; blood clotting time; chemoluminescence; comparative effectiveness; controlled study; cytotoxicity; Daboia russellii; disseminated intravascular clotting; drug efficacy; drug toxicity; ecology; ED50; envenomation; enzyme linked immunosorbent assay; extracellular trap; freeze drying; hemolysis assay; hemostasis; high performance liquid chromatography; IC50; immunoblotting; in vitro study; India; intraspecific variation; LD50; liquid chromatography-mass spectrometry; male; mass spectrometry; mouse; neurotoxicity; nonhuman; oxidative stress; particle size; point of care testing; polyacrylamide gel electrophoresis; preclinical study; protein analysis; protein degradation; protein fingerprinting; proteomics; prothrombin time; quality control; reversed phase high performance liquid chromatography; size exclusion chromatography; snakebite; thrombocyte aggregation; thromboelastography; tropical disease; animal; chemistry; Daboia russellii; ecosystem; genetics; phylogeography; snakebite; tandem mass spectrometry, Animals; Antivenins; Ecosystem; India; Male; Mice; Phylogeography; Proteome; Reptilian Proteins; Russell's Viper; Snake Bites; Tandem Mass Spectrometry; Viper Venoms
Department/Centre: Division of Biological Sciences > Centre for Ecological Sciences
Date Deposited: 11 May 2023 09:07
Last Modified: 11 May 2023 09:07
URI: https://eprints.iisc.ac.in/id/eprint/81475

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