The West Nile Virus (WNV) NS2B-NS3 protease is an attractive target for the development of therapeutics against this arboviral pathogen. In the present investigation, the screening of a small library ...of fifty-eight synthetic compounds against the NS2-NB3 protease of WNV is described. The following groups of compounds were evaluated: 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones; eugenol derivatives bearing 1,2,3-triazolic functionalities; and indan-1,3-diones with 1,2,3-triazolic functionalities. The most promising of these was a eugenol derivative, namely 4-(3-(4-allyl-2-methoxyphenoxy)-propyl)-1-(2-bromobenzyl)-1H-1,2,3-triazole (35), which inhibited the protease with IC50 of 6.86 μmol L-1. Enzyme kinetic assays showed that this derivative of eugenol presents competitive inhibition behaviour. Molecular docking calculations predicted a recognition pattern involving the residues His51 and Ser135, which are members of the catalytic triad of the WNV NS2B-NS3 protease.
Two fosmid libraries, totaling 13,200 clones, were obtained from bioreactor sludge of petroleum refinery wastewater treatment system. The library screening based on PCR and biological activity assays ...revealed more than 400 positive clones for phenol degradation. From these, 100 clones were randomly selected for pyrosequencing in order to evaluate the genetic potential of the microorganisms present in wastewater treatment plant for biodegradation, focusing mainly on novel genes and pathways of phenol and aromatic compound degradation. The sequence analysis of selected clones yielded 129,635 reads at an estimated 17-fold coverage. The phylogenetic analysis showed Burkholderiales and Rhodocyclales as the most abundant orders among the selected fosmid clones. The MG-RAST analysis revealed a broad metabolic profile with important functions for wastewater treatment, including metabolism of aromatic compounds, nitrogen, sulphur and phosphorus. The predicted 2,276 proteins included phenol hydroxylases and cathecol 2,3- dioxygenases, involved in the catabolism of aromatic compounds, such as phenol, byphenol, benzoate and phenylpropanoid. The sequencing of one fosmid insert of 33 kb unraveled the gene that permitted the host, Escherichia coli EPI300, to grow in the presence of aromatic compounds. Additionally, the comparison of the whole fosmid sequence against bacterial genomes deposited in GenBank showed that about 90% of sequence showed no identity to known sequences of Proteobacteria deposited in the NCBI database. This study surveyed the functional potential of fosmid clones for aromatic compound degradation and contributed to our knowledge of the biodegradative capacity and pathways of microbial assemblages present in refinery wastewater treatment system.
To improve a DNA vaccine containing the truncated dengue virus serotype 2 (DENV-2) envelope (E) protein and evaluate the influence of precursor membrane (prM) glycoprotein polymorphism on E protein ...immunogenicity, two vaccine candidates have been constructed by upstream insertion of the DENV-2 and DENV-3 prM genes into the DENV-2 E gene, named pCID2EtD2prM and pCID2EtD3prM, respectively. Both constructs were able to induce antibody production, which were neutralizing against DENV-2 in a murine model. Splenocytes of immunized groups, when challenged with virus, demonstrated Th1 cytokine pattern and proliferation, in addition to the increase of specific T cells. Vaccine candidates pCID2EtD2prM and pCID2EtD3prM confer 70% and 90% protection against DENV-2, respectively. The pCID2EtD3prM plasmid conferred only 40% protection in the lethal challenge with DENV-2. The results demonstrate that DENV-3 prM has a greater influence on the immunogenicity of the E protein and, probably due to its role as a chaperone, these results may be related to the correct folding and, consequently, an increase in the presentation efficiency of produced transcripts.
Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory ...response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as
, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC
) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenylfuran-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC
= 21.5 µmol·L
, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays.
In this work, the efficiency of electrochemical oxidation (EO) was investigated for removing a dye mixture containing Novacron Yellow (NY) and Remazol Red (RR) in aqueous solutions using platinum ...supported on titanium (Ti/Pt) as anode. Different current densities (20, 40 and 60 mA cm⁻²) and temperatures (25, 40 and 60 °C) were studied during electrochemical treatment. After that, the EO of each of these dyes was separately investigated. The EO of each of these dyes was performed, varying only the current density and keeping the same temperature (25 °C). The elimination of colour was monitored by UV-visible spectroscopy, and the degradation of organic compounds was analysed by means of chemical oxygen demand (COD). Data obtained from the analysis of the dye mixture showed that the EO process was effective in colour removal, in which more than 90 % was removed. In the case of COD removal, the application of a current density greater than 40 mA cm⁻² favoured the oxygen evolution reaction, and no complete oxidation was achieved. Regarding the analysis of individual anodic oxidation dyes, it was appreciated that the data for the NY were very close to the results obtained for the oxidation of the dye mixture while the RR dye achieved higher colour removal but lower COD elimination. These results suggest that the oxidation efficiency is dependent on the nature of the organic molecule, and it was confirmed by the intermediates identified.
The plant microbiota diversity is often underestimated when approaches developed mainly for the identification of cultivable microorganisms are used. High-throughput sequencing allows a deeper ...understanding of the microbial diversity associated with plants. The amplification of ITS1 was used to analyze fungal diversity in several plant organs and rhizosphere of three common bean (
Phaseolus vulgaris
) varieties grown in a greenhouse. The fungal diversity diverged between those plant organs and the rhizosphere, with the highest found in the rhizosphere and the lowest in the stem. In each organ different numbers of genus, OTUs were identified, in a total of 283 OTUs evenly distributed among the varieties. In the co-occurrence network, a larger number of positive interactions were found in the organs of the aerial part in all varieties. We observed that the diversity of the endophytic microbiota differed more between plant organs than between common bean varieties. Our results show that the diversity of endophytic fungi can be efficiently accessed with the sequencing of ITS amplicons and that this diversity may vary among distinct plant organs and the rhizosphere of a single plant variety.
operculata is a plant commonly found in the North and Northeast of Brazil. Although the regional population knows its medicinal potential, there are few scientific studies about its antimicrobial ...potential. Thus, this study aimed to characterize the proteins from L. operculata seeds extracted using different solutions and evaluate their antimicrobial potentials. The protein extracts obtained with NaCl and sodium acetate buffer presented the best inhibitory activities against Candida albicans and C. krusei. The study of the mechanism of action revealed proteins from L. operculata seeds induced pore formation on the membrane and ROS overaccumulation. Scanning Electron Microscopy images also showed severe morphological changes in Candida albicans and C. krusei. Proteins from L.operculata seeds did not show antibacterial activity. The enzymatic assays revealed the presence of proteolytic enzymes, serine and cysteine protease inhibitors, and chitinases in both protein extracts. Proteomic analysis by LC-ESI-MS/MS identified 57 proteins related to many biological processes, such as defense to (a)biotic stress, energetic metabolism, protein folding, and nucleotide metabolism. In conclusion, the L. operculata seed proteins have biotechnological potential against the human pathogenic yeasts Candida albicans and C. krusei.
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•Pathogenesis-related proteins are the abundant protein in L. operculata seed extracts.•L. operculata seed proteins present anticandidal activity against C. albicans and C. krusei.•SEM analysis revealed several damages to membrane and cell wall of both Candida cells.•Fluorescence microscopy revealed L. operculata seed proteins induced pore formation and ROS overproduction.•LC-ESI-MS/MS identified several proteins extracted from L. operculata seed.
Social inequalities are an important contributor to the global burden of disease within and between countries. Using digital technology in health promotion and healthcare is seen by some as a ...potential lever to reduce these inequalities; however, research suggests that digital technology risks re-enacting or evening widening disparities. Most research on this digital health divide focuses on a small number of social inequality indicators and stems from Western, educated, industrialized, rich, and democratic (WEIRD) countries. There is a need for systematic, international, and interdisciplinary contextualized research on the impact of social inequality indicators in digital health as well as the underlying mechanisms of this digital divide across the globe to reduce health disparities. In June 2023, eighteen multi-disciplinary researchers representing thirteen countries from six continents came together to discuss current issues in the field of digital health promotion and healthcare contributing to the digital divide. Ways that current practices in research contribute to the digital health divide were explored, including intervention development, testing, and implementation. Based on the dialogue, we provide suggestions for overcoming barriers and improving practices across disciplines, countries, and sectors. The research community must actively advocate for system-level changes regarding policy and research to reduce the digital divide and so improve digital health for all.
There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between ...efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport.
We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry.
There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons.
In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.
Dengue virus (DENV) is an arbovirus that belongs to the Flaviviridae family. Studies reveal that peptides secreted by amphibians have many functions, such as antiviral and antimicrobial activities. ...As there is no antiviral drug effective against the DENV, the antiviral activity of a synthetic peptide called HS-1, derived from the secretion of the anuran Hypsiboas semilineatus, has been evaluated. The assays of neutralization in the Vero cells show a complete inhibition of infection of the serotypes 2 and 3. Furthermore, the direct action of peptides on the viral particle can be observed through atomic force microscopy. In vivo tests display 80% protection against the dengue-2 virus due to the presence of HS-1, which reveals its potential as an antiviral against the DENV.
•The use of antimicrobial peptides (AMPs) as antivirals has increased in recent times and has shown promise.•Many molecules have been described as being able to inhibit viral replication, such as, analogs of defensins, dermaseptins, and latarcins.•On account of the lack of a vaccine and treatment against the dengue virus, it has been considered necessary to test antivirals against the dengue virus.•The results are promising against dengue-2 and dengue-3 and the antivirals tested have shown efficiency in both in vitro and in vivo experiments, in which the antiviral appears to act directly on the viral particle, disrupting the lipoprotein envelope.
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