The CDR3 region as the major driver of TREM-1 interaction with its ligands, an characterization.

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor heavily investigated in infectious and non-infectious diseases. Because of its role in amplifying inflammation, TREM-1 has been explored as a diagnostic/prognostic biomarker. Further, as the receptor has been implicated in the pathophysiology of several diseases, therapies aiming at modulating its activity represent a promising strategy to constrain uncontrolled inflammatory or infectious diseases.

Immunoinformatics-guided design of a multi-valent vaccine against Rotavirus and Norovirus (ChRNV22).

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far.

Polymorphisms in alternative oxidase genes from ecotypes of Arabidopsis and rice revealed an environment-induced linkage to altitude and rainfall.

We investigated SNPs in alternative oxidase (AOX) genes and their connection to ecotype origins (climate, altitude, and rainfall) by using genomic data sets of Arabidopsis and rice populations from 1190 and 90 ecotypes, respectively. Parameters were defined to detect non-synonymous SNPs in the AOX ORF, which revealed amino acid (AA) changes in AOX1c, AOX1d, and AOX2 from Arabidopsis and AOX1c from rice in comparison to AOX references from Columbia-0 and Japonica ecotypes, respectively. Among these AA changes, Arabidopsis AOX1c_A161E&G165R and AOX1c_R242S revealed a link to high rainfall and high altitude, respectively, while all other changes in Arabidopsis and rice AOX was connected to high altitude and rainfall.

Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors.

Histone deacetylases (HDAC) are epigenetic enzymes responsible for repressing gene expression through the deacetylation of histone lysine residues. Therefore, inhibition of HDACs has become an interesting approach for the treatment of several diseases, including cancer, hematology, neurodegenerative, immune diseases, bacterial infections, and more. Resveratrol (RVT) has pleiotropic effects, including pan-inhibition of HDAC isoforms; however, its ability to interfere with membranes requires additional optimization to eliminate nonspecific and off-target effects.

Discovery of New Zika Protease and Polymerase Inhibitors through the Open Science Collaboration Project OpenZika.

The Zika virus (ZIKV) is a neurotropic arbovirus considered a global threat to public health. Although there have been several efforts in drug discovery projects for ZIKV in recent years, there are still no antiviral drugs approved to date. Here, we describe the results of a global collaborative crowdsourced open science project, the OpenZika project, from IBM's World Community Grid (WCG), which integrates different computational and experimental strategies for advancing a drug candidate for ZIKV.

Development of New Potential Inhibitors of β1 Integrins through In Silico Methods-Screening and Computational Validation.

Integrins are transmembrane receptors that play a critical role in many biological processes which can be therapeutically modulated using integrin blockers, such as peptidomimetic ligands. This work aimed to develop new potential β1 integrin antagonists using modeled receptors based on the aligned crystallographic structures and docked with three lead compounds (BIO1211, BIO5192, and TCS2314), widely known as α4β1 antagonists. Lead-compound complex optimization was performed by keeping intact the carboxylate moiety of the ligand, adding substituents in two other regions of the molecule to increase the affinity with the target.

Investigation of Unprecedented Sites and Proposition of New Ligands for Programmed Cell Death Protein I through Molecular Dynamics with Probes and Virtual Screening.

Cancer immunotherapy has attracted increasing attention over the last few years. Programmed cell death protein 1 (PD-1) promotes self-tolerance and inhibits immune responses by modulating the T-cell function. The interaction between PD-1 and programmed cell death ligand-1 (PD-L1) leads to immune exhaustion, protecting cancer cells from destruction.

Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas.

Background: The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.

VLA-4 as a Central Target for Modulating Neuroinflammatory Disorders.

The complex steps leading to the central nervous system (CNS) inflammation and the progress to neuroinflammatory and neurodegenerative disorders have opened up new research and intervention avenues. This review focuses on the therapeutic targeting of the VLA-4 integrin to discuss the clear-cut effect on immune cell trafficking into brain tissues. Besides, we explore the possibility that blocking VLA-4 may have a relevant impact on nonmigratory activities of immune cells, such as antigen presentation and T-cell differentiation, during the neuroinflammatory process.

Computationally-obtained structural insights into the molecular interactions between Pidilizumab and binding partners DLL1 and PD-1.

Pidilizumab is a monoclonal antibody tested against several types of malignancies, such as lymphoma and metastatic melanoma, showing promising results. In 2016, the FDA put Pidilizumab's clinical studies on partial hold due to emerging evidence pointing to the antibody target uncertainty. Although initial studies indicated an interaction with the PD-1 checkpoint receptor, recent updates assert that Pidilizumab binds primarily to Notch ligand DLL1.

Antileishmanial drugs activate inflammatory signaling pathways via toll-like receptors (docking approach) from Leishmania amazonensis-infected macrophages.

The activation of proinflammatory cellular processes and signals such as those linked to NF-kB in macrophages are involved in the control of infection by Leishmania ssp. However, little is known about the influence of the drugs used in the treatment on the host cellular inflammatory signaling pathways. This study aimed to evaluate the effects of different drugs used in the treatment of leishmaniasis on inflammatory profile related to Toll-like receptors (TLRs) from L.

Differential expression of recently duplicated PTOX genes in Glycine max during plant development and stress conditions.

Plastid terminal oxidase (PTOX) is a chloroplast enzyme that catalyzes oxidation of plastoquinol (PQH) and reduction of molecular oxygen to water. Its function has been associated with carotenoid biosynthesis, chlororespiration and environmental stress responses in plants. In the majority of plant species, a single gene encodes the protein and little is known about events of PTOX gene duplication and their implication to plant metabolism.

Polymorphisms in plastoquinol oxidase (PTOX) from Arabidopsis accessions indicate SNP-induced structural variants associated with altitude and rainfall.

Plant plastoquinol oxidase (PTOX) is a chloroplast oxidoreductase involved in carotenoid biosynthesis, chlororespiration, and response to environmental stresses. The present study aimed to gain insight of the potential role of nucleotide/amino acid changes linked to environmental adaptation in PTOX gene/protein from Arabidopsis thaliana accessions. SNPs in the single-copy PTOX gene were identified in 1190 accessions of Arabidopsis using the Columbia-0 PTOX as a reference.

In silico identification of inhibitors of ribose 5-phosphate isomerase from Trypanosoma cruzi using ligand and structure based approaches.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects approximately seven million people, mainly in Latin America, and causes about 7000 deaths annually. The available treatments are unsatisfactory and search for more effective drugs against this pathogen is critical. In this context, the ribose 5-phosphate isomerase (Rpi) enzyme is a potential drug target mainly due to its function in the pentose phosphate pathway and its essentiality (previously shown in other trypanosomatids).

Plasmodium vivax Cell Traversal Protein for Ookinetes and Sporozoites (PvCelTOS) gene sequence and potential epitopes are highly conserved among isolates from different regions of Brazilian Amazon.

The Plasmodium vivax Cell-traversal protein for ookinetes and sporozoites (PvCelTOS) plays an important role in the traversal of host cells. Although essential to PvCelTOS progress as a vaccine candidate, its genetic diversity remains uncharted. Therefore, we investigated the PvCelTOS genetic polymorphism in 119 field isolates from five different regions of Brazilian Amazon (Manaus, Novo Repartimento, Porto Velho, Plácido de Castro and Oiapoque).

In silico Identification and Validation of a Linear and Naturally Immunogenic B-Cell Epitope of the Plasmodium vivax Malaria Vaccine Candidate Merozoite Surface Protein-9.

Synthetic peptide vaccines provide the advantages of safety, stability and low cost. The success of this approach is highly dependent on efficient epitope identification and synthetic strategies for efficacious delivery. In malaria, the Merozoite Surface Protein-9 of Plasmodium vivax (PvMSP9) has been considered a vaccine candidate based on the evidence that specific antibodies were able to inhibit merozoite invasion and recombinant proteins were highly immunogenic in mice and humans.

Structural and molecular modeling features of P2X receptors.

Currently, adenosine 5'-triphosphate (ATP) is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature.