Venomics of Medically Important yet Neglected Elapid Snakes of India and the Antivenomic Potential of Plant Extracts

Abstract

India is considered the world's snakebite capital, where over 58,000 snakebite fatalities are registered annually. Most bites are primarily attributed to four snake species: the spectacled cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis carinatus) that are collectively termed as the 'big four'. Recent research has unravelled a significant variation in snake venom composition and toxicity at inter- and intraspecific levels, resulting in an alarming ineffectiveness of antivenoms - the only available treatment for snakebites. However, the extent of venom variability, which often results from differing ecologies, evolutionary histories, and/or environmental conditions, remains largely uninvestigated in the majority of clinically important snakes. For example, the influence of varying ecology and environment on the venom of the common krait (B. caeruleus), the snake species with a near-pan-India distribution responsible for the second-highest number of snakebite-related deaths in India, has not been investigated to date. To address this knowledge gap, my PhD research focused on assessing the biogeographic venom variation in this species across India. Furthermore, I have evaluated the repercussions of this geographic venom variation on the preclinical efficacy of commercially available Indian antivenoms.

Similarly, the extent of intrapopulation venom variation, especially at finer geographic scales, remains poorly understood. I had, therefore, employed an interdisciplinary approach involving venom proteomics, biochemistry, and pharmacology to assess venom variation in monocled cobra (N. kaouthia) sampled across a small spatial scale (<50 km). Finally, I have evaluated the in vitro and in vivo venom binding and neutralisation capabilities of conventional antivenoms in countering toxicities inflicted by various individuals in this population.

While conventional antivenoms have saved thousands of lives, they suffer from numerous flaws, such as ineffectiveness against necrotic effects, reduced dose-effectiveness that often leads to many secondary reactions, including fatal anaphylaxis, and unavailability in many primary health centres. Secondary metabolites of plants have been shown to effectively neutralise snakebite pathologies, especially the local effects such as haemorrhage and necrosis. Therefore, I have assessed the antivenomic potential of medicinal plants, such as avaram (Cassia auriculata), utilised in traditional medicine. The neutralising potency of Cassia auriculata flower extracts against medically important snake venoms has been evaluated using in vitro experiments. Finally, I identify the active components in these plant extracts and will explore their potential role in treating snakebites in India.