About the Project
Snakebite envenomation (SBE), a high priority neglected tropical disease affects several million people worldwide resulting in as many as 150,000 deaths and around 500,000 permanent disabilities every year. Our previous study on the socio-economic impact of SBE on the rural population of Tamil Nadu, India showed the magnitude of this disaster on a typical population, which directly affected by SBE. The state-of-the-art technology used for the production of antivenom (produced in animals against snake venoms) has remained virtually unchanged for more than 100 years. This treatment is associated with several problems; a) most notably it requires refrigeration, b) it is very expensive, c) must be administered in a hospital under supervision and d) lack of efficacy with high rates of serious complications. Therefore, it is vital to identify and understand the molecular functions of venom components that are responsible for death and injury in order to develop more efficacious diagnostics and therapeutics to treat SBE.
As a team of specialists with distinctive areas of expertise, we are interested in the isolation and characterisation of various venom proteins to determine their sequence-structure-function and evolutionary relationships. This will tremendously assist in the development of specific diagnostic tools for the detection of SBE from diverse species at different regions of the world. Furthermore, since the majority of venom components are proteins (mainly enzymes), we are using organic/synthetic chemistry approach to develop novel inhibitors or repurpose existing drugs in order to block the toxic activities of venom proteins. This will facilitate the development of a combination of chemical molecules and/or drugs that could collectively be used as a ‘universal antidote’ to treat SBE worldwide. We strongly believe that the chemical-based therapeutic approach is likely to possess numerous advantages over the traditionally used antivenom therapy. Therefore, this will be a ‘life-saving gift’ for people who live in remote regions of developing countries where SBE is an everyday threat for their lives.
Students who are interested in this project will have splendid opportunities to learn a broad spectrum of techniques in the field of pharmacology, toxicology, cell and molecular biology, biochemistry, pathology, structural biology, bioinformatics, biophysics and pharmaceutical chemistry.
References
Layfield, H., Williams, H., Ravishankar, D., Mehmi, A., Sonavane, M., Salim, A., Vaiyapuri, R., Lakshminarayanan, K., Vallance, T., Bicknell, A., Trim, S., Patel, K. and Vaiyapuri, S. (2020) Repurposing cancer drugs, batimastat and marimastat, to inhibit the activity of a group I metalloprotease from the venom of the Western Diamondback rattlesnake, Crotalus atrox. Toxins. (In Press)
Williams, H., Mellows, B., Mitchell, R., Sfyri, P., Layfield, H., Salamah, M., Vaiyapuri, R., Collins-Hooper, H., Bicknell, A., Matsakas, A., Patel, K. and Vaiyapuri, S. (2019) Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. PLoS Neglected Tropical Diseases, 13 (1). e0007041.
Williams, H. F., Layfield, H. J., Vallance, T., Patel, K., Bicknell, A. B., Trim, S. A. and Vaiyapuri, S. (2019) The urgent need to develop novel strategies for the diagnosis and treatment of snakebites. Toxins, 11 (6). 363.
Williams, H. F., Hayter, P., Ravishankar, D., Baines, A., Layfield, H. J., Croucher, L., Wark, C., Bicknell, A. B., Trim, S. and Vaiyapuri, S. (2018) Impact of Naja nigricollis venom on the production of methaemoglobin. Toxins, 10 (12). 539.
Williams, H. F., Vaiyapuri, R., Gajjeraman, P., Hutchinson, G., Gibbins, J. M., Bicknell, A. B. and Vaiyapuri, S. (2017) Challenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: the views of clinicians. Toxicon, 130. pp. 44-46.
Vaiyapuri S, Vaiyapuri R, Ashokan R, Ramasamy K, Nattamaisundar K, Jeyaraj A, Chandran V, Gajjeraman P, Baksh MF, Gibbins JM, Hutchinson EG (2013) Snakebite and its socio-economic impacts on the rural population of Tamilnadu, India. PLoS One 8(11):e80090.
Vaiyapuri S, Hutchinson EG, Ali MS, Dannoura A, Stanley RG, Harrison RA, Bicknell AB, Gibbins JM (2012) Rhinocetin, a venom-derived integrin-specific antagonist inhibits collagen-induced platelet and endothelial cell functions. Journal of Biological Chemistry 287(31): 26235-44.
Vaiyapuri S, Wagstaff SC, Harrison RA, Gibbins JM, Hutchinson EG (2011) Evolutionary analysis of novel serine proteases in the venom gland transcriptome of Bitis gabonica rhinoceros. PLoS One 6(6): e21532.
Vaiyapuri S, Wagstaff SC, Watson KA, Harrison RA, Gibbins JM, et al. (2010) Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros. PLoS Neglected Tropical Diseases 4(8): e796.
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