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Hiss of death - Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy

ABSTRACT: The project aims at investigating the snake venom variability of Naja naja populations from six different biogeographic zones across India.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Naja Naja

TISSUE(S): Venom

SUBMITTER: Kartik Sunagar

LAB HEAD: Dr. Kartik Sunagar

PROVIDER: PXD020497 | Pride | 2021-02-10

REPOSITORIES: Pride

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			Action	DRS
	05112019_RID_1313_NaNaRj_F1.raw	Raw
	05112019_RID_1313_NaNaRj_F10.raw	Raw
	05112019_RID_1313_NaNaRj_F3.raw	Raw
	05112019_RID_1313_NaNaRj_F4.raw	Raw
	05112019_RID_1313_NaNaRj_F5.raw	Raw

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Project description:This project mainly aims to characterize the complex toxic components present in the venom of Indian cobra (Naja naja) from the Western Ghats of India. Naja naja (NN) is native to the Indian subcontinent and is also found in Pakistan, Sri Lanka, Bangladesh and Southern Nepal. It is a highly venomous snake species of genus Naja of the Elapidae family. They are seen in wide habitats like plains, dense or open forests, rocky terrains, wetlands, agricultural lands, and outskirts of villages and even in highly populated urban areas. This species has been included in the ‘Big 4’ category of venomous snake species that accounts for majority of morbidity and mortality cases in India. Therefore, exploring the venom proteome of Naja naja is decisive to develop and design new antivenom and therapeutics against its envenomation. The venom proteome of Naja naja was characterized through various orthogonal separation strategies and identification strategies. In order to achieve this the crude venom components were resolved on a 12% SDS page. Also, the venom was decomplexed through reversed-phase HPLC followed by SDS analysis. Further each of the bands were subjected to in-gel digestion using trypsin, chymotrypsin and V8 proteases. All the digested peptides were then subjected to Q-TOF LC-MS/MS analysis.

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Project description:BackgroundSnake venom composition is dictated by various ecological and environmental factors, and can exhibit dramatic variation across geographically disparate populations of the same species. This molecular diversity can undermine the efficacy of snakebite treatments, as antivenoms produced against venom from one population may fail to neutralise others. India is the world's snakebite hotspot, with 58,000 fatalities and 140,000 morbidities occurring annually. Spectacled cobra (Naja naja) and Russell's viper (Daboia russelii) are known to cause the majority of these envenomations, in part due to their near country-wide distributions. However, the impact of differing ecologies and environment on their venom compositions has not been comprehensively studied.MethodsHere, we used a multi-disciplinary approach consisting of venom proteomics, biochemical and pharmacological analyses, and in vivo research to comparatively analyse N. naja venoms across a broad region (>6000 km; seven populations) covering India's six distinct biogeographical zones.FindingsBy generating the most comprehensive pan-Indian proteomic and toxicity profiles to date, we unveil considerable differences in the composition, pharmacological effects and potencies of geographically-distinct venoms from this species and, through the use of immunological assays and preclinical experiments, demonstrate alarming repercussions on antivenom therapy. We find that commercially-available antivenom fails to effectively neutralise envenomations by the pan-Indian populations of N. naja, including a complete lack of neutralisation against the desert Naja population.ConclusionOur findings highlight the significant influence of ecology and environment on snake venom composition and potency, and stress the pressing need to innovate pan-India effective antivenoms to safeguard the lives, limbs and livelihoods of the country's 200,000 annual snakebite victims.

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