The
World Health Organization has declared snakebite as a neglected
tropical disease. Antivenom administration is the sole therapy against
venomous snakebite; however, several limitations of this therapy reinforce
the dire need for an alternative and/or additional treatment against
envenomation. Inhibitors against snake venoms have been explored from
natural resources and are synthesized in the laboratory; however,
repurposing of small-molecule therapeutics (SMTs) against the principal
toxins of snake venoms to inhibit their lethality and/or obnoxious
effect of envenomation has been garnering greater attention owing
to their established pharmacokinetic properties, low-risk attributes,
cost-effectiveness, ease of administration, and storage stability.
Nevertheless, SMTs are yet to be approved and commercialized for snakebite
treatment. Therefore, we have systematically reviewed and critically
analyzed the scenario of small synthetic inhibitors and repurposed
drugs against snake envenomation from 2005 to date and proposed novel
approaches and commercialization strategies for the development of
efficacious therapies against snake envenomation.
Indian Red Scorpion (Mesobuthus tamulus) stings are a neglected public health problem in tropical and sub-tropical countries, including India. The drawbacks of conventional therapies using commercial anti-scorpion antivenom (ASA) and α1-adrenoreceptor antagonists (AAA) have prompted us to search for an adequate formulation to improve treatment against M. tamulus stings. Novel therapeutic drug formulations (TDF) of low doses of commercial ASA, AAA, and ascorbic acid have remarkably improved in neutralising the in vivo toxic effects of M. tamulus venom (MTV) tested in Caenorhabditis elegans and Wistar strain albino rats in vivo models. The neutralisation of MTV-induced production of free radicals, alteration of the mitochondrial transmembrane potential, and upregulated expression of genes involved in apoptosis, detoxification, and stress response in C. elegans by TDF surpassed the same effect shown by individual components of the TDF. Further, TDF efficiently neutralized the MTV-induced increase in blood glucose level within 30 to 60 min post-treatment, organ tissue damage, necrosis, and pulmonary oedema in Wistar rats, indicating its clinical application for effecting treating M. tamulus envenomation. This study demonstrates for the first time that C. elegans can be a model organism for screening the neutralization potency of the drug molecules against a neurotoxic scorpion venom.
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