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Snakebite is a major public health concern in many parts of the world, including India, where over 58,000 deaths occur annually due to snake envenoming. The common krait (Bungarus caeruleus) is responsible for the second-highest number of snakebite-related mortalities in the country. However, despite its notoriety, little is known about its venom ecology, functions and compositional variation across bioclimatic zones, partly because these nocturnal snakes are highly elusive, making it difficult to find them in the wild. We aim to address this knowledge gap by characterising the venom composition and toxicity profiles of the pan-Indian populations (n = 8) of B. caeruleus using a combination of proteomics, receptor-toxin interaction assays, biochemical experiments, pharmacological tests and preclinical evaluations. We reveal considerable variation in venom composition, functions, and pharmacological activities among the geographically distinct populations of B. caeruleus. Furthermore, toxin-receptor interaction assays provide insights into their feeding ecology and prey-predator interactions. Finally, in vitro and in vivo experiments revealed the poor neutralising potencies of Indian antivenoms towards most populations of the common krait. Our findings highlight the alarming need to develop efficacious snakebite therapy in India to treat bites from this medically most important elapid snake. [ABSTRACT FROM AUTHOR]

Snakebite is a major public health concern in many parts of the world, including India, where over 58,000 deaths occur annually due to snake envenoming. The common krait (Bungarus caeruleus) is responsible for the second-highest number of snakebite-related mortalities in the country. However, despite its notoriety, little is known about its venom ecology, functions and compositional variation across bioclimatic zones, partly because these nocturnal snakes are highly elusive, making it difficult to find them in the wild. We aim to address this knowledge gap by characterising the venom composition and toxicity profiles of the pan-Indian populations (n = 8) of B. caeruleus using a combination of proteomics, receptor-toxin interaction assays, biochemical experiments, pharmacological tests and preclinical evaluations. We reveal considerable variation in venom composition, functions, and pharmacological activities among the geographically distinct populations of B. caeruleus. Furthermore, toxin-receptor interaction assays provide insights into their feeding ecology and prey-predator interactions. Finally, in vitro and in vivo experiments revealed the poor neutralising potencies of Indian antivenoms towards most populations of the common krait. Our findings highlight the alarming need to develop efficacious snakebite therapy in India to treat bites from this medically most important elapid snake.

Snakebite envenomation has been one of the major causes of morbidity and mortality around the world. Though intravenous administration of commercial anti-venom systemically neutralizes the toxicity, adverse effects are commonly seen in the post-treatment period. Plant metabolites and their derivatives have been shown to exhibit a wide range of antiophidian properties. In this study, we have investigated the Bungaruscaeruleus venom neutralization potential of Citrus aurantium and Citrus reticulata Blanco peels in terms of phospholipase and hemolytic inhibition. Methanolic extract of C. reticulata exhibited the highest inhibition (93%) of PLA2 activity. However, the extracts of both these Citrus species significantly inhibited the hemolytic activity of the venom (54-82%). Molecular docking indicated the binding of the citrus metabolites to catalytic site residues (TRP19, GLY30, TYR31, GLY32, and HIS48) of PLA2. In vivo studies using Swiss Albino mice confirmed the neutralising capacity of the citrus peel extract, as reflected by the increase in survival time. Therefore, the study reveals that these metabolites in the methanolic extract of the citrus peel can be used as supplements for the management of snake bites. [ABSTRACT FROM AUTHOR]

Anti-snake venom therapy is the only treatment for snake bite but leads to acute and chronic conditions which may be severe. The medicinal plants have gained importance over years to find an effective alternative to anti-snake venom. The present study focused on evaluating the potential of Clerodendrum serratum for the anti-snake venom activity. Phytochemicals were extracted from the C. serratum with different solvents. The ethyl acetate and methanolic extracts were found to neutralize the major enzyme toxins (phospholipase A2, protease and hyaluronidase) of Bungarus caeruleus and Daboia russelii venom at a concentration of 100 μg/mL. The fibrinogenolytic activity of both the venoms were neutralized. The study proves that the plant C. serratum possesses certain compounds which inhibit the toxins present in the venom of B. caeruleus and D. russelii. [ABSTRACT FROM AUTHOR]

Snake envenomations have been a serious yet often overlooked public health threat especially in tropical and subtropical countries, including Southeast Asia. The medically important venomous land snakes in Southeast Asia include snakes from the Elapidae and Crotalidae families. Among the elapids, there are only 12 species that are considered of medical importance, represented by the kraits (Bungarus caeruleus, B. candidus, B. fasciatus, B. flaviceps and B. multicinctus). The incidence of snakebite is high in India. Apart from mortality, the morbidity is due to various complications. The common krait (Bungarus caeruleus) is the most toxic snake found commonly in the plains of throughout the India and the number of snakebites in the rural areas of India was recorded by this snake. The present article highlights the prevalence and the clinical complications of Indian common krait envenomation among the rural populations of India. [ABSTRACT FROM AUTHOR]

The Ceylon krait ( Bungarus ceylonicus ) is a deadly venomous elapid snake endemic to Sri Lanka. Its habitat is mainly in the wet zone of the island. Despite its frequent encounters in and near human dwellings, reports of envenoming are rare and limited to four in the literature. The first and last fatal reports envenoming by B. ceylonicus was in 1993. After over two decades, we report two confirmed cases of B. ceylonicus bites-one a dry bite and the other with signs and symptoms of moderate envenoming. The envenoming occurred at night while the victim was asleep, causing tightness in the chest and dyspnoea on waking up, followed by neuromuscular paralysis that did not cause respiratory failure and complete recovery was observed three days following the bite. [ABSTRACT FROM AUTHOR]

Highlights: [•] BCV showed cytotoxic activity on promastigote and amastigote of Leishmania donovani in in vitro condition. [•] BCV activated macrophages and increased cytokine productions in in vitro experiments. [•] BCV treatment decreased parasite count both in liver and spleen of infected BALB/c mice. [•] BCV treatment increased production of TNF-α, IFN-γ, ROS, NO in infected mice. [•] Liver and spleen structure was partially restored due to BCV treatment in infected mice. [Copyright &y& Elsevier]

Abstract: Bungarus caeruleus (Common Krait) is a nocturnal venomous snake that is responsible for many snakebites in India. In the present study, we report the biochemical parameters involved in the neurotoxicity of the venom. The purpose of this study was to characterize the toxic enzymes and proteins in crude krait venom. The results of this study indicate that crude venom consists of proteases esterases, oxidases and nucleotidases enzymes. The highly prominent enzymes responsible for toxicity was found to be hyaluronidases and phospholipases. Crude venom on electrophoresis under reduced conditions showed more number of low molecular weight proteins than high molecular weight proteins. [Copyright &y& Elsevier]

Bungarotoxin present in Bungarus caeruleus (BC) causes life threatening respiratory muscle paralysis. Deep coma and hypokalaemia have been observed in a significant proportion of patients, but the cause is unknown. We postulate the likely mechanism behind these two phenomena. We studied clinical details of two patients admitted with deep coma and performed electroencephalograms (EEG) and brain stem auditory and visual evoked potentials (BAEP and VEP). Daily serum potassium was measured along with urinary potassium excretion as a marker of total extracellular body potassium. Both patients had no brain stem reflexes on admission and the EEG revealed absent alpha and delta activity and presence of dominant theta activity. Alpha rhythm returned on the 3rd day in one patient, while in the other it did not, and the latter patient died on the 13th day due to disseminated intravascular coagulation. BAEP were delayed and VEP were absent in the deceased patient. Both had low serum potassium and low urinary potassium excretion. Replacement of potassium (up to 1.5mmol/kg/day) did not improve serum potassium and urinary potassium excretion. Absent alpha and delta activity in EEG and delayed BAEP and absent VEP are suggestive of a central action of the venom on both the cortical and brain stem neurones. Persistently low serum potassium and reduced urinary potassium excretion are suggestive of intracellular shift as the causative mechanism of hypokalaemia. [ABSTRACT FROM AUTHOR]