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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.

Aiming at understanding the effect of the replacement of iron by ruthenium in the Protoporphyrin IX (PPIX) system of the heme group, in this work density functional theory calculations were performed to investigate the structures, nature of the M–NO bond and electronic spectra of the complexes [ M (Im)(PPIX)( L )] q , where M = Fe 2+ and Ru 2+ , Im = Imidazole ring, PPIX = Protoporphyrin IX of the heme group and L = NO + , NO and NO − . Energetic and structural results obtained at the B3LYP/SBKJC/6-31G(d) level of theory indicates that the NO coordinates preferentially through the nitrogen atom and its oxidized form NO + produces more stable complexes. Charge and energy decomposition analysis revealed that, independent of the coordination mode, the interaction of NO species with the ruthenium fragment is stronger than with iron. TD-DFT calculations predict that the transition that can lead to photodissociation of the Ru–NO bond occurs at 419 nm and if the NO coordinates to ruthenium in its oxidized form this transition is blue-shifted to 384 nm. The results obtained in this work also gives support to conclude that ruthenium complexes with the protoporphyrin IX (PPIX) system can strongly bind NO, which can be used to capture NO species, and releasing it upon irradiation with visible light.

Sodium adducts of six organosulfur-α,ω-ditetrazole compounds (Tz-(CH2)n-S(O)m-(CH2)n-Tz; where Tz = tetrazole ring; n = 2, 3; m = 0, 1, 2) were generated via electrospray ionization (ESI) and their fragmentation pattern assessed via collision-induced dissociation (CID). Two main dissociation channels were observed: (a) losses of N2 and HN3 from the tetrazole rings; (b) cleavage of the C–S bond. The sulfoxides pass predominantly through the second fragmentation pathway, but for the sulfides and sulfones the tetrazole ring fragmentation occurs. Theoretical calculations at the B3LYP/6-31 + G(d,p) level indicate that for all the adducts (sulfide, sulfoxide, and sulfone) the dissociation pathway that leads to product ions arising from loss of N2 was the most exothermic. Based on these results and assumptions, it was postulated that the dissociation of the sulfoxide adducts occurs under kinetic control (N2-loss pathway via a much more energetic transition state). For the sulfide and sulfone adducts, on the other hand, the dissociation process takes place via a thermodynamically controlled process. Copyright © 2011 John Wiley & Sons, Ltd.

A sequential Monte Carlo/Quantum Mechanics approach was used to investigate the solvent effects on d → d transition of the Ni 2+ ion in aqueous and ammonia solutions. A set of Lennard-Jones parameters were generated by modification of the UFF Force Field. The structural results obtained for the liquid structure around the Ni 2+ ion are in very good agreement with the experimental findings. The water molecules in the second coordination shell interact strongly with the first shell, with hydrogen bonds of −14.6 ± 3.3 kcal mol −1 which is 30% stronger than in the ammonia complex. The electronic spectrum was evaluated within the TD-DFT approach on the gas phase geometry and also on the Monte Carlo generated clusters, including the long range solvent effects by means of the PCM continuum model. We show that the computed electronic transitions are all red-shifted compared with the experimental results and, the agreement with the experimental values are only qualitative.

A sequential Monte Carlo/quantum mechanics approach was used to investigate the solvent effects on d → d transition of the Fe2+ ion in aqueous solution. A set of Lennard-Jones parameters were generated by modification of the UFF force field. The structural results obtained for the liquid structure around the Fe2+ ion are in very good agreement with the experimental findings. The water molecules in the second coordination shell interacts strongly with the first shell, with a hydrogen bond energy of −15.6 ± 3.0 kcal/mol, which represents about 20% of the binding energy computed for the [Fe(H2O)]2+ species. The electronic spectrum was calculated within the TD-DFT approach and we show that inclusion of outer solvation shells explicitly in the calculation does not affect appreciably the d → d transition.

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.