NMR-based metabolomics applied to ecotoxicology with zebrafish (Danio rerio) as a prominent model for metabolic profiling and biomarker discovery: Overviewing the most recent approaches.

Metabolomics is an innovative approach used in the medical, toxicological, and biological sciences. As an interdisciplinary topic, metabolomics and its relation with the environment and toxicological research are extensive. The use of substances, such as drugs and pesticides, contributes to the continuous releasing of xenobiotics into the environment, harming organisms and their habitats. In this context, fish are important bioindicators of the environmental condition and have often been used as model species. Among them, zebrafish (Danio rerio) presents itself as a versatile and straightforward option due to its unique attributes for research. Zebrafish proves to be a valuable model for toxicity assays and also for metabolomics profiling by analytical tools. Thus, NMR-based metabolomics associated with statistical analysis can reasonably assist researchers in critical factors related to discovering and validating biomarkers through accurate diagnosis. Therefore, this review aimed to report the studies that applied zebrafish as a model for (eco)toxicological assays and essentially utilized NMR-based metabolomics analysis to assess the biochemical profile and thus suggest the potential biological marker.

Molecular Docking, ADMET Analysis and Molecular Dynamics (MD) Simulation to Identify Synthetic Isoquinolines as Potential Inhibitors of SARS-CoV-2 MPRO.

BACKGROUND: The rapidly widespread SARS-CoV-2 infection has affected millions worldwide, thus becoming a global health emergency. Although vaccines are already available, there are still new COVID-19 cases daily worldwide, mainly due to low immunization coverage and the advent of new strains. Therefore, there is an utmost need for the discovery of lead compounds to treat COVID-19. OBJECTIVE: Considering the relevance of the SARS-CoV-2 MPRO in viral replication and the role of the isoquinoline moiety as a core part of several biologically relevant compounds, this study aimed to identify isoquinoline-based molecules as new drug-like compounds, aiming to develop an effective coronavirus inhibitor. METHODS: 274 isoquinoline derivatives were submitted to molecular docking interactions with SARS-CoV-2 MPRO (PDB ID: 7L0D) and drug-likeness analysis. The five best-docked isoquinoline derivatives that did not violate any of Lipinski's or Veber's parameters were submitted to ADMET analysis and molecular dynamics (MD) simulations. RESULTS: The selected compounds exhibited docking scores similar to or better than chloroquine and other isoquinolines previously reported. The fact that the compounds interact with residues that are pivotal for the enzyme's catalytic activity, and show the potential to be orally administered makes them promising drugs for treating COVID-19. CONCLUSION: Ultimately, MD simulation was performed to verify ligand-protein complex stability during the simulation period.