Peptides to Tackle Leishmaniasis: Current Status and Future Directions.

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources-amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others-or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.

A retrospective study of clinical and epidemiological characteristics of snakebite in Napo Province, Ecuadorian Amazon.

BACKGROUND: Snakebite envenoming remains a relevant public health problem in tropical and subtropical countries. In Ecuador, this is particularly true in an area of great diversity like the Amazon region. Nevertheless, there is scarce information about epidemiological and clinical characteristics of these accidents in this area. METHODS: This was a descriptive and retrospective study of snakebite cases treated at a tertiary hospital in the Napo Province, Ecuadorian Amazon, from 2015 to 2019. We collected sociodemographic and snakebite-related information, clinical aspects and the use of antivenom and antibiotics from medical records. RESULTS: Information from 133 snakebite accidents was reviewed in this time period. Reports of snakebite envenoming decreased over the years. In total, 67% of those bitten were from nearby indigenous communities, which were the most affected groups. When a species was identified, Bothrops atrox was responsible for the highest number of cases registered. Local clinical manifestations were more frequent than systemic signs, in keeping with the typical effects produced by bothropic venoms. Additionally, data showed that more antivenom vials were given than those suggested by the protocol of the Ecuadorian Ministry of Health, in proportion to the grade of severity. Finally, we identified a low incidence of adverse reactions with antivenom administration, as well as a frequent use of antibiotics. CONCLUSIONS: The profile of snakebite accidents in the Napo Province is very similar to that described for other localities in the Amazon region of Ecuador and neighboring countries, with its challenges and limitations. Such aspects underlie the importance of establishing a robust and science-based public health program to respond to this frequent, but neglected, tropical disease.

Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity.

Peptides have positively impacted the pharmaceutical industry as drugs, biomarkers, or diagnostic tools of high therapeutic value. However, only a handful have progressed to the market. Toxicity is one of the main obstacles to translating peptides into clinics. Hemolysis or hemotoxicity, the principal source of toxicity, is a natural or disease-induced event leading to the death of vital red blood cells. Initial screenings for toxicity have been widely evaluated using erythrocytes as the gold standard. More recently, many online databases filled with peptide sequences and their biological meta-data have paved the way toward hemolysis prediction using user-friendly, fast-access machine learning-driven programs. This review details the growing contributions of in silico approaches developed in the last decade for the large-scale prediction of erythrocyte lysis induced by peptides. After an overview of the pharmaceutical landscape of peptide therapeutics, we highlighted the relevance of early hemolysis studies in drug development. We emphasized the computational models and algorithms used to this end in light of historical and recent findings in this promising field. We benchmarked seven predictors using peptides from different data sets, having 7-35 amino acids in length. According to our predictions, the models have scored an accuracy over 50.42% and a minimal Matthew's correlation coefficient over 0.11. The maximum values for these statistical parameters achieved 100.0% and 1.00, respectively. Finally, strategies for optimizing peptide selectivity were described, as well as prospects for future investigations. The development of in silico predictive approaches to peptide toxicity has just started, but their important contributions clearly demonstrate their potential for peptide science and computer-aided drug design. Methodology refinement and increasing use will motivate the timely and accurate in silico identification of selective, non-toxic peptide therapeutics.