The Versatility of Serine Proteases from Brazilian Bothrops Venom: Their Roles in Snakebites and Drug Discovery

Author:

Romanazzi Marcela1,Filardi Eloise T. M.1ORCID,Pires Geovanna M. M.2,Cerveja Marcos F.1ORCID,Melo-dos-Santos Guilherme1,Oliveira Isadora S.3ORCID,Ferreira Isabela G.3ORCID,Cerni Felipe A.4,Santos-Filho Norival Alves15ORCID,Monteiro Wuelton M.6ORCID,Almeida José R.7ORCID,Vaiyapuri Sakthivel7ORCID,Pucca Manuela B.12ORCID

Affiliation:

1. Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 19060-900, Brazil

2. Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 19060-900, Brazil

3. Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 19040-903, Brazil

4. Medical School, Federal University of Roraima, Boa Vista 69310-000, Brazil

5. Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-060, Brazil

6. Department of Teaching and Research, Dr. Heitor Vieira Dourado Tropical Medicine Foundation, Manaus 69850-000, Brazil

7. School of Pharmacy, University of Reading, Reading RG6 6UB, UK

Abstract

Serine proteases are multifunctional and versatile venom components found in viper snakes, including the Bothrops species, a widely distributed genus notorious for causing the highest number of snakebites across Latin America. These enzymes, representing a significant fraction of Bothrops venom proteomes, exhibit a wide range of biological activities that influence blood coagulation, fibrinolysis, and inflammation. This review provides a comprehensive overview of serine proteases, with a particular focus on those found in the venom of Brazilian Bothrops snakes. The discussion begins with a summary of snake species found in Brazil and their medical relevance. Specifically addressing the Bothrops genus, this review explores the distribution of these species across Brazilian territory and their associated medical importance. Subsequently, the article investigates the biochemistry of Bothrops venoms and the clinical manifestations induced by envenomation. Finally, it offers an in-depth discussion on the serine proteases, highlighting their biochemical properties, mechanisms of action, and potential therapeutic applications. Furthermore, this review provides an in-depth exploration of the diverse serine proteases found in Bothrops venoms and their functional significance, from thrombin-like effects to potent fibrinogenolytic actions, which determine the clinical manifestations of envenomation. This review delves into the evolutionary adaptations and biochemical diversity of serine proteases in Bothrops venoms, emphasizing their critical roles in venom functionality and the resulting pathophysiological effects. Additionally, it opens new avenues for utilizing these enzymes in biomedical applications, underscoring their potential beyond toxinology.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Medical Research Council

Publisher

MDPI AG

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