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2025

Hiss and tell: What influences venom yields of India’s big four snakes?

We investigated how venom yield varies in India’s most medically important snakes and what drives those differences. By analysing venom from hundreds of Spectacled Cobra, Russell's Viper, Common Krait, and both subspecies of Saw-scaled Viper; South Indian and Sochurek's Saw-scaled Viper, across regions and life stages, we found that venom output depends mainly on species, age, and, in some cases, geography, rather than sex or captivity. We show that adults deliver far more venom than younger snakes and that different species balance venom quantity and potency in distinct ways. Together, these insights help explain snakebite severity and inform antivenom production and evolutionary studies of envenomation strategies.

Deadly innovations: Molecular phylogenetics and evolution of phospholipase A2 toxins in viperid snake venoms

We explored how phospholipase A₂ toxins, one of the most important components of viper venoms, have evolved over time. By reconstructing their evolutionary history, we show that these toxins have diversified repeatedly, giving rise to multiple functional forms and independent origins of neurotoxicity. We also reveal strong signals of both adaptive evolution and structural constraint shaping toxin function. Overall, we highlight venom as a dynamic evolutionary system and emphasize the need for integrated genomic and functional studies to fully understand these deadly innovations.

Dissecting Daboia: Investigating synergistic effects of Russell's viper venom toxins

The whole is deadlier than the sum of its parts. We uncovered "toxin synergy" in Russell’s viper venom, proving that metalloproteinases and phospholipases A₂ work in tandem to amplify tissue destruction. By demonstrating that breaking this partnership can neutralize lethality, we’ve opened a new door for combination therapies that go beyond traditional antivenom.

Explaining Echis: Proteotranscriptomic Profiling of Echis carinatus carinatus Venom

We provided the first comprehensive molecular and functional profile of the Indian saw-scaled viper’s venom. By combining venom gland transcriptomics with proteomic and biochemical analyses, we identified the major toxin families driving pathology and revealed variation even within a single population. We also tested venom lethality and antivenom efficacy in vivo. This work fills a major knowledge gap and strengthens the scientific foundation for improving treatment of saw-scaled viper bites.

Preclinical evaluation of small molecule inhibitors as early intervention therapeutics against Russell’s viper envenoming in India

We tested whether small molecule drugs could complement or even improve upon traditional antivenom therapy for Russell’s viper bites. Using venoms from across India, we showed that two clinically advanced inhibitors—alone and in combination—can neutralise key venom effects and prevent death, even when treatment is delayed. Our results highlight the promise of affordable, accessible, and fast-acting drugs as future frontline snakebite treatments.

Deadly innovations: Molecular phylogenetics and evolution of phospholipase A2 toxins in viperid snake venoms

We explored how phospholipase A₂ toxins, one of the most important components of viper venoms, have evolved over time. By reconstructing their evolutionary history, we show that these toxins have diversified repeatedly, giving rise to multiple functional forms and independent origins of neurotoxicity. We also reveal strong signals of both adaptive evolution and structural constraint shaping toxin function. Overall, we highlight venom as a dynamic evolutionary system and emphasize the need for integrated genomic and functional studies to fully understand these deadly innovations.

Clinical challenges, controversies, and regional strategies in snakebite care in India

We synthesised expert insights from clinicians, researchers, and policymakers to identify the major bottlenecks in snakebite care across India. Through thematic analysis, we highlighted persistent clinical challenges, debated controversial practices, and emphasised the need for region-specific antivenoms and stronger peripheral healthcare systems. This work provides practical guidance for policy reform, training, and research prioritisation to improve snakebite outcomes nationwide.

Significant Serpents: Predictive Modelling of Bioclimatic Venom Variation in Russell’s Viper

We explored how climate shapes venom function in the world’s most medically important snake. By linking venom enzymatic activity to temperature and rainfall patterns across India, we showed that environmental factors partly explain regional differences in Russell’s viper venom. Using predictive models, we mapped venom phenotypes across the species’ range. These insights connect ecology, evolution, and medicine, and can guide region-specific treatment strategies.

2024

Structural analysis of an Asterias rubens peptide indicates the presence of a disulfide-directed β-hairpin fold

We revealed that the sea star peptide KASH2 adopts a rare disulfide-directed β-hairpin fold, a structure previously thought to be limited to arachnids. Our findings suggest this fold arose through convergent evolution and may play a role in injury responses in sea stars. Although KASH2 did not promote human wound healing in vitro, our work expands understanding of the evolutionary diversity and potential functions of disulfide-rich peptides.

Elusive elapids: biogeographic venom variation in Indian kraits and its repercussion on snakebite therapy

Traveling across India reveals a hidden danger: the venom of the common krait is not the same everywhere. By integrating proteomics and pharmacology, we discovered that kraits in different regions vary so much that current "standard" antivenoms fail to recognize many of them. This research identifies a critical gap in the safety net for millions of people.

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

As a snake grows, its "chemical toolkit" often undergoes a total transformation. We tracked these changes from birth to adulthood in India’s deadliest species. While cobras remain consistent, newborn Russell’s vipers possess a remarkably more potent venom than their parents—a shift driven by the changing demands of their prey and environment.

Harnessing the Cross-Neutralisation Potential of Existing Antivenoms for Mitigating Snakebite in Sub-Saharan Africa

We showed that an existing polyvalent antivenom can neutralise the venoms of many medically important African snakes for which no specific treatments exist. Using preclinical models, we demonstrated strong cross-neutralisation across species and regions. This work offers an immediately deployable strategy to reduce snakebite deaths while next-generation antivenoms are still in development.

Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins

We looked to nature's own receptors to design a better shield. By mimicking how the human body interacts with toxins, we engineered a synthetic antibody that neutralizes deadly α-neurotoxins across multiple snake species. This "universal" approach provides a modern blueprint for replacing animal-derived antivenoms with lab-grown, monoclonal solutions.

2023

The Royal Armoury: Venomics and antivenomics of king cobra (Ophiophagus hannah) from the Western Ghats

Despite the King Cobra's fame, its venom in India remained a mystery—until now. We delivered the most comprehensive profile of Western Ghats populations and discovered a troubling reality: existing Indian and Thai antivenoms provide zero protection against their bite. Our work provides the data needed to begin closing this treatment gap.

Fangs in the Ghats: Preclinical insights into the medical importance of pit vipers from the Western Ghats

Small vipers are often overlooked, but their clinical impact is anything but minor. We demonstrated that pit vipers from the Western Ghats cause severe systemic effects, including kidney failure. Because these "neglected" species aren't used in antivenom production, we’ve highlighted a significant risk to local populations that requires immediate medical policy shifts.

The deep-rooted origin of disulfide-rich spider venom toxins

We traced the origin of most spider venom toxins back to a single ancient molecular scaffold that emerged over 375 million years ago. By identifying dozens of new toxin families, we showed that spiders rely on a shared ancestral blueprint, unlike other venomous animals. Our findings reveal how venom function and deployment shape evolutionary diversification across one of the largest venomous lineages on Earth.

2022

Stings on wings: Proteotranscriptomic and biochemical profiling of the lesser banded hornet (Vespa affinis) venom

Snake venoms aren't the only potent chemical weapons in the animal kingdom. We profiled the lesser banded hornet and found that wasp toxins can actually outperform snake toxins in specific biochemical tasks. This research shifts the focus toward wasps as a rich, underexplored source for both defensive evolution studies and drug discovery.

The deadly toxin arsenal of the tree-dwelling Australian funnel-web spiders.

We unravelled why tree-dwelling funnel-web spiders cause especially severe envenomation by profiling their venom composition and activity. We discovered unique toxin families and showed that their venoms strongly modulate human ion channels, explaining their clinical severity. Our work sheds light on how habitat shifts shape venom evolution and potency.

The Middle Eastern Cousin: Comparative Venomics of Daboia palaestinae and Daboia russelii.

Why is the Russell's viper a global killer while its closest relative is not? We compared these two vipers side-by-side to solve this puzzle. While their venom glands look similar, their chemical "cocktails" differ dramatically in toxicity and biological activity, explaining the vast difference in their clinical impact on humans.

Contextual constraints: dynamic evolution of snake venom phospholipase A2.

We re-evaluated the evolution of phospholipase A₂ toxins by integrating ecology, structure, and lineage history. We showed that PLA₂ evolution is shaped not only by positive selection but also by strong functional constraints and lineage-specific ecological pressures. This work reframes how major venom toxin families diversify over time.

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

We demonstrated that simple purification of existing antivenoms can dramatically improve their effectiveness. Our second-generation antivenom showed superior venom recognition, higher dose efficiency, and improved neutralisation of toxic effects from India’s ‘big four’ snakes. This approach offers a practical pathway to safer and more effective snakebite treatment.

2021

Venomics of the enigmatic Andaman cobra (N. sagittifera) and the preclinical failure of Indian antivenoms in Andaman and Nicobar Islands.

Island isolation has created a venom that our current medicine cannot touch. We profiled the Andaman cobra and found that standard antivenoms are completely ineffective against it. This isn't just a scientific curiosity; it's a call for region-specific antivenom production to protect the people of the Andaman and Nicobar Islands.

Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance.

We proposed an ecological and evolutionary framework for understanding snakebite envenoming as a biological interaction rather than a purely clinical event. By integrating venomics, antivenomics, and evolutionary theory, we show how ecological context can inform better snakebite treatment strategies. This work bridges basic science and public health.

Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India's snakebite problem.

We revealed striking venom variation within a single cobra population sampled over less than 50 km. We showed that even fine-scale variation can strongly affect venom toxicity and antivenom efficacy. These findings expose a hidden challenge in snakebite management and emphasise the need to consider rapid evolutionary processes in therapy design.

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

We showed that Russell’s viper venom varies substantially across India in composition, activity, and potency. While commercial antivenoms neutralised most populations reasonably well, they performed poorly against venoms from northern semi-arid regions. Our findings highlight how regional venom variation can undermine therapy and stress the need for pan-India effective antivenoms, especially in snakebite hotspots.

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.)

We synthesised current knowledge on the origin and early evolution of snakes, drawing on fossil, molecular, and ecological evidence. By placing venom evolution within this broader evolutionary framework, we highlighted how early squamate diversification shaped modern snake biology. This work provides a foundation for understanding how venom systems emerged and diversified.

Evolution bites: Timeworn inefficacious snakebite therapy in the era of recombinant vaccines.

We reviewed how ecological and evolutionary forces drive venom variation and expose the shortcomings of conventional animal-derived antivenoms. We highlighted why current Indian antivenoms often fail and discussed the promise of recombinant and next-generation therapies. This work calls for a paradigm shift in how snakebite treatment is designed and delivered.

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

We generated the most comprehensive pan-Indian venom profile of the spectacled cobra to date and uncovered striking geographic differences in venom composition and toxicity. We demonstrated that commercially available antivenoms often fail to neutralise these diverse venoms, including complete failure against desert populations. Our findings underscore the urgent need for region-specific or pan-India efficacious snakebite therapies.

The Curious Case of the “Neurotoxic Skink”: Scientific Literature Points to the Absence of Venom in Scincidae

We debunked a high-profile claim of a "venomous skink" by proving the symptoms were actually caused by a krait. This paper serves as a vital reminder for clinicians to rely on evidence over anecdote, ensuring patients receive the correct treatment in life-or-death situations.

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

We uncovered hidden diversity among Indian kraits and revealed how post-genomic regulation, rather than gene content alone, drives dramatic venom differences. Despite similar venom gland transcriptomes, venom composition and toxicity varied widely among cryptic species. Our results explain why current antivenoms fail against many krait bites and highlight the need for regionally effective therapies.

2020

Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators

Why would a spider evolve a toxin that kills a human, a creature it doesn't eat? We solved this riddle by tracing the evolution of δ-hexatoxins. Our data reveals these deadly peptides didn't evolve for us; they were a defensive adaptation against vertebrate predators that accidentally turned humans into "collateral damage."

Causes and consequences of medically-important snake venom variation.

Venom is a moving target, and that is a nightmare for modern medicine. This review breaks down the biological machinery that causes venom to vary across species and environments. By understanding the "why" behind this diversity, we’ve mapped out a new strategy for developing antivenoms that are resilient to evolutionary change.

The POU domain transcription factor NvPOU4/Brain3 is required for the terminal differentiation of neural cells in Nematostella vectensis.

To understand the human brain, we looked at the simple sea anemone. We identified the "master switch" protein, NvPOU4, which dictates how nerve cells mature. This discovery suggests that the genetic blueprint for building a nervous system has remained largely unchanged for hundreds of millions of years.

2019

Beyond the ‘big four’: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies.

India’s antivenom is built for four snakes, but the country is home to dozens of killers. We profiled "neglected" species like the Sochurek’s saw-scaled viper and revealed that current treatments are often powerless against them. This work serves as an evidence-based demand for a more inclusive, regionally-aware antivenom strategy.

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals.

Venom isn't just for reptiles; it has been "invented" by mammals too. By sequencing the genome of the rare solenodon, we proved that these mammals evolved venom independently from snakes. This study highlights a fascinating case of "molecular convergence," where nature uses the same tools to solve the same predatory problems.

2018

Arthropod venoms: Biochemistry, Ecology and Evolution.

From the deepest oceans to your backyard, arthropods have conquered the planet with chemical warfare. We synthesized decades of research to show how venom has fueled the success of insects and spiders. This review frames these venoms not just as toxins, but as a massive, underexplored library for the next generation of life-saving drugs.

Cell type-specific expression profiling unravels the development and evolution of stinging cells in sea anemone.

We mapped the gene expression programs underlying the formation of cnidocytes, the iconic stinging cells of cnidarians. Using cell-specific transcriptomics, we showed that cnidocyte development involves dramatic transcriptional shifts and the recruitment of conserved stress-response regulators. Our findings reveal how evolutionary novelty arises through repurposing ancient genetic machinery.

Scratching the Surface of an Itch: Molecular Evolution of Aculeata Venom Allergens

Why does a bee sting cause a minor itch for some and a life-threatening reaction for others? We analyzed the molecular evolution of insect allergens and found that most are strictly preserved by evolution. This provides a clear molecular framework for researchers working to solve the global problem of venom-induced anaphylaxis.

Animal Venoms: Origin, Diversity and Evolution

We reviewed how venoms have evolved repeatedly across the animal kingdom, often converging on similar molecular solutions despite independent origins. We highlighted the ecological drivers of venom diversity and their dual role as agents of harm and sources of lifesaving drugs. This work frames venoms as both evolutionary innovations and biomedical resources.

Dynamics of venom composition across a complex life cycle

A sea anemone is a different animal at every stage of its life—and so is its venom. We showed that as these creatures grow, their venom shifts to match their changing needs for predation and defense. This finding challenges the old idea that venom is a static "signature" of a species.

2016

Ecological venomics: how genomics, transcriptomics and proteomics can shed new light on the ecology and evolution of venom

The lab bench has moved into the wild. We explored how the "omics" revolution—genomics, transcriptomics, and proteomics—has turned venom research into a powerful tool for understanding ecology. By looking at venom through this high-tech lens, we can now "read" a snake’s evolutionary history directly from its venom gland.

Deep venomics of the Pseudonaja genus reveals inter- and intra-specific variation.

To find the deadliest secrets, you have to look deeper than ever before. Using "deep venomics," we uncovered hidden diversity in Australian brown snakes that traditional methods missed. We identified novel toxins and unusual "sugared" peptides, proving that even well-studied snakes still have surprises waiting for us.

2015

The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals

The idea that venom always evolves at lightning speed is a myth. By analyzing thousands of toxin sequences, we proposed a "two-speed" model of evolution. While young lineages innovate rapidly to survive, ancient groups actually enter long periods of evolutionary "stasis" where their venom remains unchanged for millions of years.

Kartik Sunagar © 2026

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