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Biogeographic venom variation in medically important Indian snakes and the inadequacy of antivenom therapy in snakebite hotspots

ABSTRACT: The project aims at investigating the snake venom variability of Daboia russelii populations from five different biogeographic zones across India.

INSTRUMENT(S):

ORGANISM(S): Daboia Russelii

TISSUE(S): Venom

SUBMITTER: Kartik Sunagar

LAB HEAD: Dr. Kartik Sunagar

PROVIDER: PXD021060 | Pride | 2021-02-26

REPOSITORIES: Pride

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			Action	DRS
	DaRuMH.pep.xml	Pepxml
	DaRuMH_F1.raw	Raw
	DaRuMH_F10.raw	Raw
	DaRuMH_F2.raw	Raw
	DaRuMH_F3.raw	Raw

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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

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

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From birth to bite: the evolutionary ecology of India's medically most important snake venoms

Project description:Venoms of N. naja and D. russelii individuals of various developmental stages, including neonates (<30 days), juveniles (between 1 to 12 months), and mature individuals (>36 months), were sampled with permission from the state forest department of Karnataka. 226 individuals and 9 clutches were examined, including periodic venom collection (every three months) from the same N. naja and D. russelii juvenile individuals to track ontogenetic changes across time. Freshly collected venoms were flash-frozen in liquid nitrogen, lyophilised and stored at -80° C. Venoms were fractionated using RP-HPLC and SDS-PAGE and subjected to tandem mass spectrometry for toxin identification. The relative abundance of each toxin family were estimated and compared across different developmental stages.

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The Arabian cousin: Comparative venomics of Daboia palaestinae and Daboia russelii

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A wolf in another wolf’s clothing: Post-genomic regulation dictates venom profiles of medically-important cryptic kraits in India

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Fangs in the ghats: preclinical insights into the medical importance of endemic pit vipers from the Western Ghats

Project description:The socioeconomic burden of snakebite in India is largely attributed to the ‘big four’ snakes, completely neglecting the considerable impact of envenoming by many other snake species. Bites from the so-called ‘neglected many’ are often treated with a polyvalent antivenom that is manufactured against the ‘big four’ snakes - a strategy that has been widely documented to fail. Yet, specific antivenoms are not commercially manufactured against these snakes. While the medical importance of various species of cobras, saw-scaled vipers, and kraits is very well-known, the clinical impact of pit vipers from the rainforests of the Western Ghats, northeastern India, and Andaman and Nicobar islands has remained elusive. Amongst the 90+ species of snakes found in the Western Ghats, the hump-nosed (Hypnale hypnale), Malabar (Craspedocephalus malabaricus) and bamboo (Craspedocephalus gramineus) pit vipers can potentially inflict clinically severe envenoming in humans. To evaluate the severity of toxicity inflicted by these snakes, we characterised their venom composition, biochemical and pharmacological activities, and toxicity- and morbidity-inducing potentials. Our findings highlight the therapeutic inadequacies of the generic Indian and Hypnale-specific Sri Lankan polyvalent antivenoms in neutralising morbidity and mortality resulting from pit viper envenomings and underscore the need for a regional antivenom therapy in India.

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Lachesis muta snake venom peptidome

Project description:Snake venoms are known to be major sources of peptides with different pharmacological properties. In this study, we comprehensively explored the venom peptidomes of three specimens of Lachesis muta, the largest venomous snake in South America, using mass spectrometry techniques. The analysis revealed 19 main chromatographic peaks common to all specimens. A total of 151 peptides were identified, including 69 from a metalloproteinase, 58 from the BPP-CNP precursor, and 24 from a L-amino acid oxidase. To our knowledge, 126 of these peptides were reported for the first time in this work, including a new SVMP-derived peptide fragment, Lm-10a. Our findings highlight the dynamic nature of toxin maturation in snake venoms, driven by proteolytic processing, post-translational modifications, and cryptide formation.

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Project description:In this study, we unveil the venom composition, biochemistry, pharmacological activity, and potency of the Andaman cobra (N. sagittifera).

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Elusive elapid: Biogeographic venom variation in Indian kraits and its repercussion on snakebite therapy

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2024-11-02 | PXD052611 | Pride

The preclinical evaluation of a second-generation antivenom for treating snake envenoming in India

Project description:In this study, by employing chromatographic purification of the bulk, we have significantly enhanced the preclinical performance of the conventional Indian antivenom product. The effectiveness of the test batches of this ‘second-generation’ antivenom was evaluated using a variety of in vitro and in vivo preclinical assays, including venom recognition and toxicity and pathology neutralisation. The outcomes of these experiments demonstrated the significantly superior performance of the purified product over all other major commercial Indian antivenoms.

2022-04-04 | PXD029436 | Pride

Comparative gender peptidomics of Bothrops atrox venoms: new peptides and evidences of increased disintegrins levels in the venoms of females

Project description:Background: Bothrops atrox is known to be the pitviper responsible for most snakebites and human fatalities in the Amazon region. It can be found in a wide geographical area including the northern South America, the east of Andes and the Amazon basin. Possibly due to its wide distribution range and generalist feeding, intraspecific venom variation was reported by previous proteomics studies. Sex-based and ontogenetic variations on venom compositions of Bothrops snakes were also subject of proteomic and peptidomic analysis. However, the venom peptidome of B. atrox remains unknown. Methods: we conducted a mass spectrometry-based analysis of the venom peptides of individual male and female specimens combining bottom-up and top-down approaches. Results: We identified in B. atrox a total of 105 native peptides in the mass range of 0.4 to 13.9 kDa. Quantitative analysis showed that Phospholipase A2 and Bradykinin Potentiating Peptides were the most abundant peptide families in both genders, but the disintegrins levels were significantly increased in the venoms of females. Known peptides processed at non-canonical sites and new peptides were also revealed in this work. Conclusion: The venom peptidomes of male and female specimens of B. atrox were analyzed by mass spectrometry-based approaches in this work. The study points to differences in the disintegrin levels in the venoms of females that may result in distinct pathophysiology in envenomation. Further research is needed to explore its biological implications.

2020-10-13 | PXD018632 | Pride

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