Snake venoms are complex cocktails of non-toxic and toxic molecules that work synergistically for the envenoming outcome. Alongside the immediate consequences, chronic manifestations and long-term sequelae can occur. Recently, extracellular vesicles (EVs) were found in snake venom. EVs mediate cellular communication through long distances, delivering proteins and nucleic acids that modulate the recipient cell’s function. However, the biological roles of snake venom EVs, including possible cross-organism communication, are still unknown. This knowledge may expand the understanding of envenoming mechanisms. In the present study, we isolated and characterized the EVs from Bothrops jararaca venom (Bj-EVs), giving insights into their biological roles. Fresh venom was submitted to differential centrifugation, resulting in two EV populations with typical morphology and size range. Several conserved EV markers and a subset of venom related EV markers, represented mainly by processing enzymes, were identified by proteomic analysis. The most abundant protein family observed in Bj-EVs was 5’-nucleotidase, known to be immunosuppressive and a low abundant and ubiquitous toxin in snake venoms. Additionally, we demonstrated that mammalian cells efficiently internalize Bj-EVs. The commercial antibothropic antivenom partially recognizes Bj-EVs and inhibits cellular EV uptake. Based on the proteomic results and the in vitro interaction assays using macrophages and muscle cells, we propose that Bj-EVs may be involved not only in venom production and processing but also in host immune modulation and long-term effects of envenoming.

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Leishmaniasis is one of the most important neglected tropical diseases. The chemotherapy for its treatment uses very toxic compounds with a low efficacy rate. Thus, there is an urgent need to develop new chemotherapeutic agents to help countries control this devasting disease. In drug development, different approaches can be used to identify potential cellular targets that allow us to understand better the cell biology of eukaryotic cells. Several groups are dedicated to studying new molecules, searching for promising candidates against Leishmania. Different techniques have been used to characterize the cell biology, biochemistry, and molecular biology alterations induced by the treatments, trying to understand the mechanisms of action. The main goal of this chapter is to describe an overview of the literature exploring the several studies published about the chemotherapy of anti-Leishmania concerning the mechanisms of action of different classes of molecules or therapeutic alternatives.