Monomeric Esterase: Insights into Cooperative Behavior, Hysteresis/Allokairy.

Herein, we present a novel esterase enzyme, Ade1, isolated from a metagenomic library of Amazonian dark earths soils, demonstrating its broad substrate promiscuity by hydrolyzing ester bonds linked to aliphatic groups. The three-dimensional structure of the enzyme was solved in the presence and absence of substrate (tributyrin), revealing its classification within the α/β-hydrolase superfamily. Despite being a monomeric enzyme, enzymatic assays reveal a cooperative behavior with a sigmoidal profile (initial velocities vs substrate concentrations).

Cooperative and structural relationships of the trimeric Spike with infectivity and antibody escape of the strains Delta (B.1.617.2) and Omicron (BA.2, BA.5, and BQ.1).

Herein, we conducted simulations of trimeric Spike from several SARS-CoV-2 variants of concern (Delta and Omicron sub-variants BA.2, BA.5, and BQ.

Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron is currently the most prevalent SARS-CoV-2 variant worldwide. Herein, we calculated molecular dynamics simulations of the trimeric spike and Spike for 300 ns. Our results show that Spike has more conformational flexibility than Spike.

Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures in some countries to contain the spread of the disease has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread remain unclear.

Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease.

Selenium-Derivative Compounds: A Review of New Perspectives in the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-β (Aβ) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD.

Antioxidant Activity, Molecular Docking, Quantum Studies and Antinociceptive Activity of Sulfonamides Derived From Carvacrol.

The synthesis and antioxidant, antinociceptive and antiedematogenic activities of sulfonamides derived from carvacrol-a druglike natural product-are reported. The compounds showed promising antioxidant activity, and sulfonamide derived from morpholine () demonstrated excellent antinociceptive and antiedematogenic activities, with no sedation or motor impairment. The mechanism that underlies the carvacrol and derived sulfonamides' relieving effects on pain has not yet been fully elucidated, however, this study shows that the antinociceptive activity can be partially mediated by the antagonism of glutamatergic signaling.

Quantitative structure-activity relationships, molecular docking and molecular dynamics simulations reveal drug repurposing candidates as potent SARS-CoV-2 main protease inhibitors.

The current outbreak of COVID-19 is leading an unprecedented scientific effort focusing on targeting SARS-CoV-2 proteins critical for its viral replication. Herein, we performed high-throughput virtual screening of more than eleven thousand FDA-approved drugs using backpropagation-based artificial neural networks ( = 0.60, = 0.

Structure-activity relationships of sulfonamides derived from carvacrol and their potential for the treatment of Alzheimer's disease.

Five synthetic sulfonamides derived from carvacrol, a natural product and a small molecule with druglike properties, were evaluated with respect to their effects on the cognitive deficits of animals with streptozotocin (STZ)-induced Alzheimer's disease (AD). Memory, ambulation, anxiety and oxidative stress were evaluated. assays were performed to assess the inhibition of acetylcholinesterase (AChE), and the data were combined with molecular docking for the establishment of structure-activity relationships.

Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti- Activity.

Small-molecule compounds that have promising activity against macromolecular targets from occasionally fail when tested in whole-cell phenotypic assays. This outcome can be attributed to many factors, including inadequate physicochemical and pharmacokinetic properties. Unsuitable physicochemical profiles usually result in molecules with a poor ability to cross cell membranes.

Development of a pharmacophore for cruzain using oxadiazoles as virtual molecular probes: quantitative structure-activity relationship studies.

Chagas's is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. According to the World Health Organization, 7 million people are infected worldwide leading to 7000 deaths per year. Drugs available, nifurtimox and benzimidazole, are limited due to low efficacy and high toxicity.