The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor α (ERα). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2–infected hamsters localized lung pathology with increased ERα lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ERα and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ERα interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology.

The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein. Herein, we employed microsecond-long molecular dynamics simulations to study the impact of the mutations of the S glycoprotein in SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7), termed the “UK variant”, in comparison with the wild type, with the aim to decipher the structural basis of the reported increased infectivity and virulence. The simulations provided insights on the different dynamics of UK and wild-type S glycoprotein, regarding in particular the Receptor Binding Domain (RBD). In addition, we investigated the role of glycans in modulating the conformational transitions of the RBD. The overall results showed that the UK mutant experiences higher flexibility in the RBD with respect to wild type; this behavior might be correlated with the increased transmission reported for this variant. Our work also adds useful structural information on antigenic “hotspots” and epitopes targeted by neutralizing antibodies.

A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional coordinates, and the molecular dynamics trajectories of the SARS-CoV-2 spike protein and its main variants. The Spike Mutants website can serve as a rapid online tool for investigating the impact of novel mutations on virus fitness. Taking into account the high variability of SARS-CoV-2, this application can help the scientific community when prioritizing molecules for experimental assays, thus, accelerating the identification of promising drug candidates for COVID-19 treatment. Below we describe the main features of the platform and illustrate the possible applications for speeding up the drug discovery process and hypothesize new effective strategies to overcome the recurrent mutations in SARS-CoV-2 genome.

Organophosphorus compounds (OP) are mainly used in agriculture as pesticides. Unfortunately, each year many rural workers are intoxicated by these compounds and, many times, the diagnosis of the exact molecule causing the intoxication can be tardy, exposing the patients to a huge risk of death. One way of preventing this delay is the use of enzymatic biosensors like the enzyme Esterase 2 from Alicyclobacillus acidocaldarius (AaEST2), which is an efficient fluorescent biosensor for OP identification. However, although this enzyme has been well studied experimentally, the complete understanding of the energy transfer processes that occur between AaEST2 and OPs is still obscure, making it difficult the accurate identification of the OP. In order to better understand this process, we applied in this work molecular docking and molecular dynamics studies, together with the Förster fluorescence resonance energy transfer (FRET) theory, to achieve a better understanding of the fluorescence profiles that are described in the literature and correlate them to individual OPs. Our results suggest that the pesticides chlorpyrifos, diazinon, parathion and paraoxon are all capable of quenching the residue Trp85 from AaEST2, triggering fluorescence. This supports our hypothesis that AaEST2 can be used as a fluorescent biosensor for the detection of organophosphorus compounds.