From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery

Autor(es):Mostrar menos -

Figueiredo Bordon, Karla de Castro ^[1] ; Cologna, Camila Takeno ^[1] ; Fornari-Baldo, Elisa Correa ^[2] ; Pinheiro-Junior, Ernesto Lopes ^[1] ; Cerni, Felipe Augusto ^[1] ; Amorim, Fernanda Gobbi ^[3] ; Pino Anjolette, Fernando Antonio ^[4] ; Cordeiro, Francielle Almeida ^[1] ; Wiezel, Gisele Adriano ^[1] ; Cardoso, Iara Aime ^[1] ; Ferreira, Isabela Gobbo ^[1] ; de Oliveira, Isadora Sousa ^[1] ; Boldrini-Franca, Johara ^[5] ; Pucca, Manuela Berto ^[6] ; Baldo, Mateus Amaral ^[2] ; Arantes, Eliane Candiani ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept BioMol Sci, Lab Anim Toxins, Ribeirao Preto - Brazil

^[2] Univ Paulista, Hlth & Sci Inst, Sao Jose Do Rio Preto - Brazil

^[3] Vila Velha Univ, Postgrad Program Pharmaceut Sci, Vila Velha - Brazil

^[4] Fed Inst Educ Sci & Technol Parana, Dept Pharm, Palmas - Brazil

^[5] Vila Velha Univ, Postgrad Program Ecosyst Ecol, Vila Velha - Brazil

^[6] Univ Fed Roraima, Med Sch, Boa Vista, Parana - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 11, JUL 24 2020.
• Citações Web of Science: 14

Resumo

Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic targets, drug libraries, prototypes for the design of drugs, cosmeceuticals, and therapeutic agents. However, making these molecules applicable requires extensive preclinical trials, with some applications also demanding clinical trials, in order to validate their molecular target, mechanism of action, effective dose, potential adverse effects, as well as other fundamental parameters. Here we go through the pitfalls for a toxin-based potential therapeutic drug to become eligible for clinical trials and marketing. The manuscript also presents an overview of the current picture for several molecules from different animal venoms and poisons (such as those from amphibians, cone snails, hymenopterans, scorpions, sea anemones, snakes, spiders, tetraodontiformes, bats, and shrews) that have been used in clinical trials. Advances and perspectives on the therapeutic potential of molecules from other underexploited animals, such as caterpillars and ticks, are also reported. The challenges faced during the lengthy and costly preclinical and clinical studies and how to overcome these hindrances are also discussed for that drug candidates going to the bedside. It covers most of the drugs developed using toxins, the molecules that have failed and those that are currently in clinical trials. The article presents a detailed overview of toxins that have been used as therapeutic agents, including their discovery, formulation, dosage, indications, main adverse effects, and pregnancy and breastfeeding prescription warnings. Toxins in diagnosis, as well as cosmeceuticals and atypical therapies (bee venom and leech therapies) are also reported. The level of cumulative and detailed information provided in this review may help pharmacists, physicians, biotechnologists, pharmacologists, and scientists interested in toxinology, drug discovery, and development of toxin-based products. (AU)

• Processo FAPESP: 17/14035-1 - Melhoramento de fragmentos de anticorpos humanos (scFVs) específicos para peçonhas animais
• Beneficiário: Felipe Augusto Cerni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/00586-6 - Caracterização de um inibidor de fosfolipase A2 da glândula de peçonha de Crotalus durissus terrificus: um possível adjuvante na terapia do envenenamento
• Beneficiário: Gisele Adriano Wiezel
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/14158-9 - Melhoramento de fragmentos de anticorpos humanos (scFvs) específicos para peçonhas animais
• Beneficiário: Felipe Augusto Cerni
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 19/10173-6 - Produção, modificação e caracterização de toxinas animais com potencial aplicação biotecnológica
• Beneficiário: Eliane Candiani Arantes Braga
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/21233-7 - Análises por espectrometria de massas de uma nova fosfodiesterase da peçonha de Crotalus durissus collilineatus
• Beneficiário: Isadora Sousa de Oliveira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 17/04724-4 - Melhoramento de fragmentos de anticorpos humanos (scFVs) específicos para peçonhas animais
• Beneficiário: Eliane Candiani Arantes Braga
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/26619-7 - Estudo proteômico comparativo das peçonhas branca e amarela de Crotalus durissus terrificus, com ênfase nas enzimas hialuronidase e L-aminoácido oxidase
• Beneficiário: Karla de Castro Figueiredo Bordon
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 16/04761-4 - Caracterização estrutural, funcional e análise da resposta imune in vivo de uma serinoprotease recombinante de Crotalus durissus collilineatus modificada por PEGlação
• Beneficiário: Ernesto Lopes Pinheiro Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/03580-9 - Avaliação bioquímica, estrutural e funcional de uma fosfodiesterase da peçonha de Crotalus durissus collilineatus
• Beneficiário: Isadora Sousa de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/26200-6 - Plataforma Venômica: Proteoma, Transcriptoma, Clonagem e Expressão de toxinas de interesse biotecnológico presentes na peçonha de Pachycondyla villosa
• Beneficiário: Camila Takeno Cologna
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado