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Venom is a complex mixture of biomolecules produced by specialized glands or cells in venomous animals. It is actively delivered to a target organism to aid in prey capture or self-defense against predators. Venom has been a key factor in the evolutionary success of many animal lineages and has independently evolved over 100 times. In our lab, we study venomous animals and their venoms as model systems to explore important questions in genetics, ecology, and evolution. Below is a brief overview of some of the main research areas in our lab.

 

Antiquated antivenoms

Each year, snakebites cause over 58,000 deaths in India. Additionally, four times that number suffer permanent disabilities, such as amputations of digits and limbs. The majority of snakebite victims are farmers from rural areas, who often serve as the primary earners for their families. As a result, snakebites devastate entire households and exert a significant negative impact on the nation’s economy.

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Snakebites are treated with antivenoms, which are produced by immunizing horses with snake venoms to generate anti-toxin antibodies. Our research has shown that snake venoms vary greatly in composition and potency, not only between different species (Senji et al. 2019, 2021a, 2021b; Attarde et al. 2021), but also among populations of the same species (Sunagar et al. 2014) and even between individual snakes within a single population over a small geographic area (Rashmi et al. 2021).

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Despite this extensive geographic variation, Indian antivenoms are still manufactured using venom from a single snake population located in two districts of Tamil Nadu in Southern India. Our studies reveal that these antivenoms often fail to neutralize the considerable venom diversity in Indian snakes (Senji et al. 2019, 2021a, 2021b; Kaur et al. 2020; Attarde et al. 2021). Furthermore, Indian antivenoms target only the so-called ‘big four’ snake species, leaving many other medically important snakes without specific antivenom treatments. Our findings underscore the urgent need for more effective snakebite therapies to save lives, prevent disabilities, and protect the livelihoods of hundreds of thousands of Indians every year.

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• Senji Laxme RR, Khochare S, DeSouza HF, Ahuja B, Suranse V, Martin G, Whitaker R and Sunagar K. 2019. Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies. PLOS Neglected Tropical Diseases.

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• Senji Laxme RR, Attarde S, Khochare S, Suranse V, Martin G, Casewell NRC, Whitaker R, and Sunagar K. 2021. Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy. PLOS Neglected Tropical Diseases.

 

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

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• Rashmi U, Khochare S, Attarde S, Senji Laxme RR, Suranse V, Martin G and Sunagar K. 2021. Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India's snakebite problem. Journal of Proteomics.

 

 

Enhancing the efficacy of conventional antivenoms​​

The antivenom manufacturing strategy has remained largely unchanged for over a century (Kaur et al. 2020). The Evolutionary Venomics Lab is actively collaborating with several established Indian antivenom producers to improve current antivenom production methods and rapidly enhance the efficacy of Indian antivenoms.

 

• Attarde S, Iyer A, Khochare S, Shaligram U, Vikharankar M and Sunagar K. The preclinical evaluation of a second-generation antivenom for treating snake envenoming in India. Toxins. 2022.​

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Discovery and expression of recombinant antivenoms

Supported by funding from various national and international agencies and in collaboration with partners, such as the International AIDS Vaccine Initiative (USA) and the Liverpool School of Tropical Medicine (UK), we are focused on discovering and recombinantly expressing broadly neutralizing antibodies. These antibodies are sourced from various animals, including rabbits, camels, cows, baboons, and horses, immunized with snake venoms from India and sub-Saharan Africa. Cutting-edge techniques in yeast display selection, B cell sorting, recombinant toxin production, and antibody engineering are central to advancing these projects.

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• Casewell NRC, Jackson TMW, Laustsen A, and Sunagar K. 2020. Causes and consequences of medically-important snake venom variation. Trends in Pharmacological Sciences.

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Alternative treatments for snakebite​​

Our research has shown the effectiveness of small molecule inhibitors in treating snakebites in India. We demonstrated that existing drugs, originally developed for other diseases, can be repurposed to reduce snakebite mortality and morbidity.

 

• Rudresha G. V., Khochare S, Casewell NR, and Sunagar K. 2025. Preclinical evaluation of small molecule inhibitors as early-intervention therapeutics against the pan-Indian Russell’s viper (Daboia russelii) envenoming. Nature communications Biology (In Press).

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Snakebite diagnostics​

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Evolutionary ecology of venoms

The evolution of venom is closely connected to the ecology and environment of the venomous animal. The impact of these factors on the venoms of animals in the Indian subcontinent remains largely unexplored. To fill this knowledge gap, we have been studying how various ecological and environmental factors influence the composition, biochemical activity, potency, and evolutionary patterns of venom in snakes, spiders, scorpions, centipedes, and many other lesser-known lineages.

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• Sunagar K, Khochare S, Senji Laxme RR, Attarde S, Dam P, Suranse V, Khaire A, Martin G, and Captain A. 2021. A wolf in another wolf’s clothing: Post-genomic regulation dictates venom profiles of medically-important cryptic kraits in India. Toxins.

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• Suranse V, Iyer A, Jackson TNW and Sunagar K@. 2021. Origin and Early Diversification of the Enigmatic Squamate Venom Cocktail. A Contribution to the Origin and Early Evolution of Snakes (D. Gower and H. Zaher Ed.). Systematics Association Special Volume Series. Cambridge University Press (in Press).

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• Attarde S, Khochare S, Iyer A, Dam P, Martin G and Sunagar K. Venomics of the enigmatic Andaman cobra (N. sagittifera) and the preclinical failure of Indian antivenoms in Andaman and Nicobar Islands. Frontiers in Pharmacology.

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Population genetics, phylogenetics and phylogeography of venomous animals

India’s diverse topography supports a vast array of biodiversity, including many venomous species. However, these species groups have not yet been thoroughly examined within a molecular phylogenetic framework. Comprehensive studies of these organisms could lead to the discovery of new species previously unknown to science and offer valuable insights into the evolutionary relationships and distribution patterns of venomous animals. Additionally, there is a significant lack of research on population structures resulting from local adaptations and the genetic diversity of venomous species. Our lab utilizes phylogenetic, phylogeographic, comparative genomics and population genetics tools to address these aforementioned shortcomings. These findings can inform conservation strategies and support the development of policies guided by ecological and evolutionary principles to protect these organisms.

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Molecular evolution of venom

Determining the evolutionary origins of venom and the molecular mechanisms driving its diversification are amongst the key research focuses of our lab. Through a combination of experimental and bioinformatic methods, including comparative genomics and evolutionary analyses, we strive to uncover the fundamental principles that transform non-toxic physiological proteins into some of the most powerful toxins known.​​

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• Suranse V, Jackson T. N. W. and Sunagar K. Contextual constraints: dynamic evolution of snake venom phospholipase A2. Toxins (in Press).

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• Sunagar K and Moran Y. The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals. 2015. PLoS Genetics. 11(10): e1005596.

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• Herzig V*, Sunagar K*, Wilson DR, Pineda SS, Israel MR, Duterte S, McFarland BS,  Undheim EAB, Hodgson WC, Alewood PF, Lewis RJ, Bosmans F, Vetter I, King GF  and Fry BG. 2020. Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators. Proceedings of the National Academy of Sciences.

 

• Sunagar K, Jackson TNW, Undheim EAB, Ali S, Antunes A and Fry BG. 2013. Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins. Toxins. 5:2172-2208.

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