A multidisciplinary study of the intraspecific variability of snake venom and its impact on the pathophysiology of envenomation and serum neutralization

• Grant number: 24/14920-9
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Karen de Morais Zani
• Grantee: Karen de Morais Zani
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: André Gustavo Tempone Cardoso ; Luis Roberto de Camargo Gonçalves ; Marisa Maria Teixeira da Rocha ; Mychel Raony Paiva Teixeira Morais ; Rafael Stuani Floriano ; Sávio Stefanini Sant Anna

Abstract

Snake envenomation is classified by the World Health Organization as a neglected tropical disease. In Brazil, 25,115 cases of snakebites by venomous snake species were recorded in 2023. Around 87% of these accidents are attributed to snakes of the genus Bothrops whereas 10% are attributed to the genus Crotalus. Snake venoms are complex mixtures of proteins, with variable composition among genera, species, subspecies, populations and individuals, subjected to Darwinian evolution. This intraspecific variability associated with their functional diversity is particularly critical when we consider the pathophysiology of envenomation and its reactivity with the antivenom. Because of its pathophysiological, ecological and evolutionary relevance, our group has been describing intraspecific phenotypic variations in the venom of species of the genera Bothrops and Crotalus. In this context, we demonstrate the presence of geographic variation in the individual profile of toxins in the venom of Crotalus durissus terrificus and Crotalus durissus collilineatus, especially in relation to the composition of phospholipase A2 (PLA2). Additionally, we have also identified different venom phenotypes of Bothrops jararaca species in relation to snake venom metalloproteinases (SVMP) content. Considering the complexity of the envenoming caused by the genera Bothrops and Crotalus and the importance of these snakes for public health, carrying out a multifaceted study correlating the phenotypic variability of the venoms to their pathophysiological variation, as well as their neutralization by the antivenom produced is of great relevance, both from a pharmacological and ecological/evolutionary point of view. Therefore, the present project proposes to characterize the composition and functional aspects of the different phenotypes of the venom of B. jararaca and C. durissus ssp., as well as to evaluate their reactivity and neutralization by the antivenom serum produced by the Butantan Institute. (AU)