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

Karla de Castro Figueiredo Bordon, Camila Takeno Cologna, Elisa Corrêa Fornari-Baldo, Ernesto Lopes Pinheiro-Júnior, Felipe Augusto Cerni, Fernanda Gobbi Amorim, Fernando Antonio Pino Anjolette, Francielle Almeida Cordeiro, Gisele Adriano Wiezel, Iara Aimê Cardoso, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Johara Boldrini-França, Manuela Berto Pucca, Mateus Amaral Baldo and Eliane Candiani Arantes.

Animal poisons and venoms are comprised of different classes of molecules displayingwide-ranging pharmacological activities. This review aims to provide an in-depth view oftoxin-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 someapplications also demanding clinical trials, in order to validate their molecular target,mechanism of action, effective dose, potential adverse effects, as well as otherfundamental parameters. Here we go through the pitfalls for a toxin-based potentialtherapeutic drug to become eligible for clinical trials and marketing. The manuscript alsopresents an overview of the current picture for several molecules from different animalvenoms and poisons (such as those from amphibians, cone snails, hymenopterans,scorpions, sea anemones, snakes, spiders, tetraodontiformes, bats, and shrews) thathave been used in clinical trials. Advances and perspectives on the therapeutic potential ofmolecules from other underexploited animals, such as caterpillars and ticks, are alsoreported. The challenges faced during the lengthy and costly preclinical and clinicalstudies and how to overcome these hindrances are also discussed for that drugcandidates 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 articlepresents a detailed overview of toxins that have been used as therapeutic agents,including their discovery, formulation, dosage, indications, main adverse effects, andpregnancy 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 helppharmacists, physicians, biotechnologists, pharmacologists, and scientists interested intoxinology, drug discovery, and development of toxin-based products.