To identify natural bioactive compounds (NBCs) as potential inhibitors of spike (S1) by means of in silico assays. NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening and molecular docking to identify those with higher affinity to the spike protein. Eight machine learning models were used to validate the results: Principal Component Analysis (PCA), Artificial Neural Network (ANN), Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Partial Least Squares-Discriminant Analysis (PLS-DA), Gradient Boosted Tree Discriminant Analysis (XGBoostDA), Soft Independent Modelling of Class Analogies (SIMCA) and Logistic Regression Discriminate Analysis (LREG). Selected NBCs were submitted to drug-likeness prediction using Lipinski’s and Veber’s rule of five. A prediction of pharmacokinetic parameters and toxicity was also performed (ADMET). Antivirals currently used for COVID-19 (remdesivir and molnupiravir) were used as a comparator. A total of 170,906 compounds were analyzed. Of these, 34 showed greater affinity with the S1 (affinity energy < -7 kcal mol-1). Most of these compounds belonged to the class of coumarins (benzopyrones), presenting a benzene ring fused to a lactone (group of heterosides). The PLS-DA model was able to reproduce the results of the virtual screening and molecular docking (accuracy of 97.0%). Of the 34 compounds, only NBC5 (feselol), NBC14, NBC15 and NBC27 had better results in ADMET predictions. These had similar binding affinity to S1 when compared to remdesivir and molnupirvir. Feselol and three other NBCs were the most promising candidates for treating COVID-19. In vitro and in vivo studies are needed to confirm these findings.

Resumen Objectivo. Evaluar el perfil microbiológico de siete centros de recogida de semen porcino (BS) en el sur de Brasil, así como evaluar la susceptibilidad antimicrobiana a la mayoría de los microorganismos encontrados en los BS. Material y métodos. El análisis bacteriológico se realizó en muestras del sistema de purificación de agua, diluyentes de semen, semen crudo y almacenado, bancos de laboratorio y otras superficies de trabajo. Resultados. El crecimiento de una población bacteriana mixta se observó en muestras de agua de todas las BS excepto una. Aproximadamente el 85% de la BS tenía contaminación significativa en sus superficies de trabajo con al menos un contaminante bacteriano. Un total de 86% de muestras de semen crudo fueron contaminadas con una o más bacterias diferentes, mientras que el 100% de BS proporcionaron muestras contaminadas. La susceptibilidad bacteriana a agentes antimicrobianos varió en más del 80% para gentamicina, neomicina y ceftiofur a 40% o menos para penicilina y lincomicina. Conclusiones. La identificación de los puntos críticos proporciona el apoyo necesario para idear mejores estrategias para minimizar la contaminación en CRSP. Además, la evaluación del nivel de resistencia a los antimicrobianos ofrece información precisa para formular protocolos antibacterianos más eficientes que tengan en cuenta el uso racional de los antibióticos.

Abstract Objective. To assess the microbiological profile in seven Boar Studs (BS) in Southern Brazil, as well as evaluate antimicrobial susceptibility response to most commonly found microorganisms in BS. Material and methods. Bacteriologic analysis was carried out in samples from the water purification system, semen extender, raw and stored semen, lab benches, and other working surfaces. Results. Growth of a mixed bacterial population was observed in water samples from all but one BS. Approximately 85% of the BS had significant contamination on their working surfaces with at least one bacterial contaminant. A total of 86% of raw semen samples were contaminated with one or more different bacteria, while 100% of the boar studs provided contaminated samples. Bacterial susceptibility to antimicrobial agents varied from over 80% for gentamycin, neomycin and ceftiofur to 40% or less for penicillin and lincomycin. Conclusions. The identification of the critical points provides necessary support to devise better strategies to minimize contamination in BS. Also, assessing the level of antimicrobial drug resistance offers accurate information to formulate more efficient antibacterial protocols that closely observe the rational use of antibiotics.

O objetivo deste estudo foi avaliar a relação entre lesões testiculares e os níveis hormonais em ratos infectados experimentalmente por Trypanosoma evansi. Para isso, a mensuração de hormônios reprodutivos, histopatologia e biomarcadores de lesão celular foi realizada em 24 animais, que foram divididos em dois grupos com 12 animais cada. Grupo A foi usado como controle negativo, não infectado, enquanto o grupo B foi composto por animais infectados com T. evansi. Ambos os grupos foram divididos em dois subgrupos (n=6), então soro e fragmentos testiculares foram colhidos no dia 5 (A1 e B1) e 15 (A2 e B2) pósinfecção (PI). A análise morfológica mostrou aumento de alterações de cabeça e cauda de espermatozóides em ratos infectados quando comparados aos do grupo controle. Uma redução significativa (P<0,01) nos níveis de LH, FSH, estradiol e testosterone associado com um aumento do cortisol foi observada no soro dos ratos do grupo B quando comparado com grupo A. Além disso, o NOx, peroxidação lipídica e oxidação proteica foram elevados nos testículos, indicando a ocorrência de lesão celular. Pela histopatologia foi possível observar uma degeneração testicular, entre outras alterações nos animais infectados. Portanto, com base nestes resultados é possível concluir que a infecção experimental por T. evansi causou mudanças nos níveis dos principais hormônios em ratos machos associados com lesão celular.

The aim of this study was to evaluate the relationship between testicular lesions and hormone levels in rats experimentally infected with Trypanosoma evansi. For that, the measurement of reproductive hormones, histopathology and biomarkers of cellular injury were carried out in twenty-four animals, which were divided into two groups with 12 animals each. Group A was the negative control, or uninfected, while group B was composed by animals infected with T. evansi. Both groups were divided again into two other subgroups (n=6), from which serum and testicular fragments were collected on days 5 (A1 and B1) and 15 (A2 and B2) post-infection (PI). The morphological analysis showed increased alterations of head and tail of sperm in infected rats when compared with those of the control group. A significant reduction (P<0.01) in the levels of LH, FSH, testosterone and estradiol, associated with an increase in cortisol, was observed in serum of group B when compared with negative control. Additionally, NOx, lipid peroxidation and protein oxidation were enhanced in testicles, indicating the occurrence of cellular lesion. On histopathology, it was possible to observe testicular degeneration, among other disorders in infected animals. Therefore, based on these results, it is possible to conclude that the experimental infection with T. evansi caused changes in the levels of the main hormones of male rats associated with cellular injury.