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Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (-8.18 kcal/mol) and VRSA (-8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies.
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INTRODUCTION: The human T-cell lymphotropic virus type 1 (HTLV-1) is aetiologically linked to myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukaemia (ATL) besides other less incident pathologies, while the type 2 has not been definitively linked to any diseases. OBJECTIVES: To determine the HTLV-1/2 seroprevalence in two Brazilian communities in northern Brazil. METHODS: In 2010 and 2015, HTLV-1/2 serological surveys were carried out in the Oiapoque county at the Brazilian border with French Guiana and in Santa Cruz do Arari, Marajó Island. Serum and breast-milk samples from 317 women (pregnant, lactating and non-pregnant non-lactating) resident in the Oiapoque county, together with serum samples from 217 females and 70 males living in Santa Cruz do Arari county, were twice screened by two distinct commercial immunoassay methods for antibodies to HTLV-1/2. Seroreactivity was confirmed by a commercial Western blot technique. Participants were interviewed for data concerning their health, socioeconomic and educational status. RESULTS: None of the Oiapoque women, mostly young and descendants of migrants, had antibodies to HTLV-1/2, despite the high HTLV-1 prevalence in neighbouring French Guiana and Caribbean Islands, while five females and three males living in Santa Cruz do Arari county were HTLV-1 infected as confirmed by Western blot testing. In contrast, the Santa Cruz do Arari community lives in relative isolation and is descended mostly from black African people with high consanguinity. CONCLUSION: Despite the proximity between Oiapoque and Santa Cruz do Arari counties, ethnic, age differences, community isolation and consanguinity may explain the distinct HTLV-1/2 epidemiology in these areas of northern Brazil.
RESUMEN
Aeromonas hydrophila is causing substantial economic losses in world aquaculture. This study determined the tolerance limit (LD50-96h) of A. hydrophila in Arapaima gigas, and also investigated the clinical signs after intradermal inoculation. Arapaima gigas fingerlings were inoculated intraperitoneally with 0 (control), 1.0×10(5), 1.0×10(6), 1.0×10(7), 1.0×10(9) and 1.0×10(10)CFU/mL of A. hydrophila for the determination of LD50-96h, which was 1.8×10(8)CFU/mL. In another trial with intradermal inoculation of 1.8×10(8)CFU/mL A. hydrophila, there was a 91.6% of mortality between 8 and 23h, and several clinical signs were found. As follows: depigmentation in the tegument, lesions in the tail and fins, loss of balance, reduction of respiratory movements, hemorrhagic foci, necrotic hemorrhages in the kidney, liver and swim bladder, splenomegaly, ascites in the abdominal cavity and hyperemia, enlargement of the gall bladder, among other clinical signs observed. The results showed that A. gigas has a relative tolerance to A. hydrophila when compared to other Neotropical fish species.
