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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.

Introduction Despite the widespread use of antivenom for the treatment of snakebite envenoming in the Indian subcontinent, the ideal dose of antivenom has been a point of contention. Low-dose regimens can economize on a scarce resource in low- and middle-income countries. This study assessed the effectiveness of a low-dose (10 vials) antivenom regimen compared to the usual 20 vials in patients with krait bite neuroparalysis requiring mechanical ventilation. Methods This study was a prospective controlled pilot study conducted in a tertiary-care hospital in north India. Participants were eligible if they were ≥12 years old, had krait bite neurotoxicity, showed severe paralysis requiring mechanical ventilation, and had access to antivenom therapy within 24 h of the bite. The primary outcome was the duration of mechanical ventilation, and the secondary outcomes were the length of hospital stay and in-hospital survival. Results Fifteen patients received 10 vials of antivenom, and 25 received 20 vials. The two treatment groups had similar baseline demographics, clinical and laboratory features, snakebite severity scores, and median time from snakebite to initiation of antivenom therapy. The low-dose regimen was as effective as the standard dose concerning the median duration of mechanical ventilation (41 h vs. 55 h, P  = 0.094), the median length of stay (78 h vs. 85.5 h, P  = 0.360), and in-hospital deaths (1 vs. 3, P  = 1.000). The incidence of ventilator-associated pneumonia was similar between the two groups (1 vs 3, P  = 1.000). Conclusion A low dose of antivenom effectively treats patients with severe krait bite neuroparalysis. [ABSTRACT FROM AUTHOR]

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]

Areca catechu seeds and their extract/s are currently used to treat various ailments and infections including snakebites. The purpose of this investigation was to assess the inhibiting/neutralizing effect of ethyl acetate and aqueous ethanolic seed extracts of A. catechu on Bungarus caeruleus (krait) venom. The enzyme activities and their inhibition were evaluated using standard procedures (in vitro). In vivo studies were conducted using chick embryos and murine models. The extracts inhibited hyaluronidase and phospholipase A2 activities. Protease activity was neutralized by the aqueous ethanolic extract only. The IC50 value of aqueous ethanolic extract for hyaluronidase was 0.001 g/mL, while that for the ethyl acetate extract for phospholipase A2 was 0.006 g/mL. In addition, both the extracts neutralized the indirect hemolysis and fibrinogenolytic activity induced by B. caeruleus venom. The LD50 for the chick embryos was 4.9 µg/egg. The 50 and 100 µg aqueous ethanolic extracts neutralized the LD50 and the challenging dose (3LD50) of venom effectively in the chick embryo model. The LD50 of B. caeruleus venom in mice was 0.1927 µg/kg; the extract extended the survival time of the mice from 25 min to 30 and 35 min in 1:10 and 1:20 ((w/w) venom:extract) ratios, respectively. The extract also neutralized myotoxic activity. The A. catechu seed extract showed promising inhibitory properties against B. caeruleus venom. In this regard, academia and industries should work collaboratively to develop and formulate a cost-effective first-aid drug. [ABSTRACT FROM AUTHOR]