The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

Abstract

Snake envenoming afflicts the Indian subcontinent with the highest rates of mortality (47,000) and morbidity globally. The only effective treatment for snakebites is the administration of antivenom, which is produced by the hyperimmunisation of equines. Commercial Indian antivenoms, however, have been shown to exhibit a poor preclinical performance in neutralising venom, as a result of inter- and intrapopulation snake venom variation. Additionally, their poor dose effectiveness necessitates the administration of larger volumes of antivenom for treatment, leading to several harmful side effects in snakebite victims, including serum sickness and fatal anaphylaxis. In this study, we employed chromatographic purification to enhance the dose efficacy of commercial Indian antivenoms. The efficacy of this ‘second-generation’ antivenom was comparatively evaluated against six other marketed antivenoms using a number of in vitro and in vivo preclinical assays, which revealed its superior venom recognition capability. Enhanced purity also resulted in significant improvements in dose effectiveness, as the ‘second-generation’ antivenom exhibited a 3 to 4.5 times increased venom neutralisation potential. Furthermore, preclinical assays revealed the increased effectiveness of the ‘second-generation’ antivenom in countering morbid effects inflicted by the ‘big four’ Indian snakes. Thus, we demonstrate the role of simpler purification steps in significantly enhancing the effectiveness of snakebite therapy in regions that are most affected by snakebites.

Fangs in the Ghats: Preclinical Insights into the Medical Importance of Pit Vipers from the Western Ghats

“…In line with this observation, the haemorrhagic activity of C. malabaricus venom tested here (MHD = 0.365 µg/mouse) was 6.5 times that of H. hypnale (MHD = 2.32 µg/mouse). Moreover, the haemorrhagic potential was found to be between two to ten times that of E. carinatus (MHD = 0.44 µg/mouse) and D. russelii (MHD = 2.19 µg/mouse), respectively [39]. Moreover, all three pit viper venoms were documented to be highly myotoxic (Supplementary Figure S4).…”

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

“…Sub-Saharan Africa (sSA) alone contributes to one-fifth of the global snakebite statistics, with ~32,000 deaths annually [2,3]. Currently, the only available therapy for snakebite is the conventional antivenom produced via the hyperimmunisation of equines with the target snake venoms [4][5][6][7]. Although a handful of antivenom products are currently marketed to treat snake envenoming in sSA, they only target a few medically relevant species [8].…”