Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and produce lethal pores in microorganisms, including protozoan pathogens, whereas others act on internal targets or by modulation of the host immune system. Protozoan parasites cause some serious life-threatening diseases among millions of people worldwide, mostly affecting the poorest in developing tropical regions. Humans can be infected with protozoan parasites belonging to the genera Trypanosoma, Leishmania, Plasmodium, and Toxoplasma, responsible for Chagas disease, human African trypanosomiasis, leishmaniasis, malaria, and toxoplasmosis. There is not yet any cure or vaccine for these illnesses, and the current antiprotozoal chemotherapeutic compounds are inefficient and toxic and have been in clinical use for decades, which increases drug resistance. In this review, we will present an overview of AMPs, the diverse modes of action of AMPs on protozoan targets, and the prospection of novel AMPs isolated from venomous arthropods with the potential to become novel clinical agents to treat protozoan-borne diseases.

Hundreds of toxins, particularly from scorpions of lesser medical significance, remain unknown, especially those from species endemic to specific ecosystems, such as Tityus fasciolatus. Their discovery could contribute to the development of new drugs for channelopathies and other diseases. Tf5 is a new peptide that has been identified from the venom of Tityus fasciolatus, a scorpion species endemic to the Brazilian Cerrado ecosystem. A full-length cDNA sequence of the Tf5 gene was obtained through a previously constructed transcriptomic library, where an ORF (Open Reading Frame) sequence with a length of 180 was found, including the 37 aa mature KTx domain, which has six Cys residues. Tf5 was purified from the crude venom, resulting in a peptide with a molecular mass of 3983.95 Da. Its K⁺ channel blocker activity was evaluated on Kv1.1, Kv1.2, Kv1.3, and Kv1.4 subtypes. Of these Kv channels, the peptide demonstrated an ability to block Kv1.2 and Kv1.3 with an IC₅₀ of 15.53 nM and 116.41 nM, respectively. Additionally, Tf5 shares a high degree of sequence identity with toxins from the α-KTx4 subfamily, which led to it being classified as α-KTx4.9. This is the first Kv channel blocker described from the T. fasciolatus scorpion.