Protein-coding gene interaction network prediction of bioactive plant compound action against SARS-CoV-2: a novel hypothesis using bioinformatics analysis.

This study aimed to verify the action of bioactive compounds from Brazilian plants on the leader genes involved in the SARS-CoV-2 pathway. The main human genes involved were identified in GeneCards and UNIPROT platforms, and an interaction network between leader genes was established in the STRING database. To design chemo-biology interactome networks and elucidate the interplay between genes related to the disease and bioactive plant compounds, the metasearch engine STITCH 3.1 was used. The analysis revealed that SMAD3 and CASP3 genes are leader genes, suggesting that the mechanism of action of the virus on host cells is associated with the molecular effects of these genes. Furthermore, the bioactive plant compounds, such as ascorbate, benzoquinone, ellagic acid, and resveratrol was identified as a promising adjuvant for the treatment inhibiting CASP3-mediated apoptosis. Bioactive plant compounds were verified as the main pathways enriched with KEGG and related to viral infection, assessments/immune/infections, and cell proliferation, which are potentially used for respiratory viral infections. The best-ranked molecule docked in the CASP3 binding site was rutin, while the SMAD3 binding site was resveratrol. In conclusion, this work identified several bioactive compounds from Brazilian plants showing potential antiviral functions that can directly or indirectly inhibit the new coronavirus.

Ligand exchange reaction involving Ru(III) compounds in aqueous solution: a hybrid quantum mechanical/effective fragment potential study.

In this work, the hybrid density functional theory/effective fragment potential (DFT/EFP) approach was applied to investigate the ligand exchange reactions [Ru(NH(3))(4)(Cl)(L)](2+)(aq)+H(2)O→[Ru(NH(3))(4)(H(2)O)(L)](3+)(aq)+Cl(-)(aq) in solution, with L= NH(3) and pyridine (Py). A procedure to generate the EFP water clusters is described. The reaction proceeds through an interchange mechanism with dissociative character, I(d), and displays a high sensitivity to the basicity of the ligand trans to the chloride. Changing the nature of the nitrogenated ligand has a drastic impact on the activation and reaction energy. When ammonia is used, the activation energy, computed at the B3LYP/cc-pVDZ/EFP level of theory is 22.7 kcal/mol, which is ∼40% higher than the value of 13.4 kcal/mol computed when for L=Py. In addition, the spontaneity of the reaction changes upon changing the nature of the nitrogenated ligand. Changing the level of theory used in the QM part of the calculation from B3LYP/cc-PVDZ to MP2/cc-pVTZ does not change the results appreciably, and inclusion of long-range effects by means of the polarizable continuum model has a negligible effect on the energetic of the reaction. The activation enthalpy computed at the B3LYP/cc-pVDZ/EFP is in very good agreement with the experimental findings, attesting to the validity of the QM/EFP approach used in this work.