Determination of the effective doses for neutralizing the main in vitro activities of Bothrops matogrossensis snake venom by antivenom

• Grant number: 25/02053-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Karen de Morais Zani
• Grantee: Isadora Busin Carneiro
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Snakebite envenoming is classified as a Neglected Tropical Disease by the World Health Organization, primarily affecting impoverished populations in rural areas of Africa, Asia, and Latin America. In Brazil, 25,115 snakebite cases were reported in 2023, 86% of which were caused by the Bothrops genus. The severity of snakebite accidents caused by Bothrops species is a significant public health issue in the country, with a considerable impact on the morbidity of those affected. The venom of these snakes consists of a complex mixture of toxins, including metalloproteinases, phospholipases A2, and serine proteases, which are responsible for severe pathophysiological effects, such as hemorrhage and coagulation disorders. The only effective treatment for snakebite envenoming is antivenom therapy. Although Bothrops antivenom can reverse systemic effects of envenomation, local effects are rarely neutralized. Due to its medical relevance, venom neutralization and immunorecognition by specific antivenoms are extensively studied. However, various studies indicate a discrepancy between results obtained in in vitro tests and the clinical efficacy observed in vivo. While antivenom effectively reverses the physiological effects of envenomation, it is often inefficient at neutralizing specific enzymatic activities in the proportions recommended by the manufacturer. This lack of direct correlation highlights the challenges in studying antivenom efficacy. Thus, this proposal aims to determine the effective dose of Bothrops antivenom produced by the Butantan Institute for neutralizing the specific enzymatic activities of Bothrops matogrossensis venom. It will also correlate these findings with proteomic data, lethality neutralization, and immunorecognition (third-generation antivenomics) previously determined by our group. The goal is to contribute to the understanding of the mechanisms involved in neutralizing the activities of Bothrops venom by Bothrops antivenom.