Dra. Gerli-Candia, Lorena

SARS-CoV-2 is the pandemic disease-causing agent COVID-19 with high infection rates. Despite the progress made in vaccine development, there is an urgent need for the identification of antiviral compounds that can tackle better the different phases of SARS-CoV-2. The main protease (Mpro or 3CLpro) of SARS-CoV-2 has a crucial role in viral replication and transcription. In this study, an in silico method was executed to elucidate the inhibitory potential of the synthesized 6-tert-octyl and 6-8-ditert-butyl coumarin compounds against the major protease of SARS-CoV-2 by comprehensive molecular docking and density functional theory (DFT), ADMET properties and molecular dynamics simulation approaches. Both compounds shown favorable interactions with the 3CLpro of the virus. From DFT calculations, HOMO-LUMO values and global descriptors indicated promising results for these compounds. Furthermore, molecular dynamics studies revealed that these ligand-receptor complexes remain stable during simulations and both compounds showed considerably high binding affinity to the main SARS-CoV-2 protease. The results of the study suggest that the coumarin compounds 6-tert-octyl and 6-8-ditert-butyl could be considered as promising scaffolds for the development of potential COVID-19 inhibitors after further studies.

The identification of drugs against the new coronavirus (SARS-CoV-2) is an important requirement. Natural products are substances that serve as sources of beneficial chemical molecules for the development of effective therapies. In this study, 187 natural compounds from Algerian herbal medicines were docked in the active site of SARS-CoV-2 main protease. The result indicates that Piperitol, Warfarin, cis-calamenen-10-ol and α-Cadinene are the structures with best affinity in the binding site of the studied enzyme and all of them respect the conditions mentioned in Lipinski’s rule and have acceptable ADMET proprieties; so, these compounds could have more potent antiviral treatment of COVID-19 than the studied compounds, and they have important pharmacokinetic properties and bioavailability.

Electronic structure calculations were performed to analyze the effectiveness of linking agents (sulfur and nitrogen) in connecting the trans-azobenzene sandwiched between two gold surfaces (Au-atoms). It was analyzed the dynamics of the load carrier and the electronic structure of the molecular backbone by applying an external electric field (EF), also a detailed structural, frontier orbital and natural bond orbital analysis (NBO) were performed. From the NBO analysis, it was possible to predict the path of charge flow in the molecular system. Electrostatic potential mapping allowed us to visualize the charge redistribution in the molecular system caused by the EF application. Our results indicate that when the nitrogen atom is used as a linking agent, the azo group of molecules may enhance their conductivity.

Derivatives of parent molecules possess similar structural activity which makes them to be the topic of equal interest. In the present work, a naturally occurring acid eugenol and its co derivatives allyl-2-methoxy-4-nitrophenol and 5-Allyl-3-nitrobenzene-1,2-diol are theoretically investigated for their antioxidant role using density functional theory (DFT). Becke’s exchange correlation functional B3LYP and Minnesota functional M062X along with the basis set 6-311++G(d,p) are used to investigate the structural property through geometry optimization, frontier molecular orbital analysis, electrostatic potential analysis, and molecular descriptive parameters. Electron donating capability of the molecules is analyzed using frontier molecular orbital analysis and molecular descriptors. Molecular surface potential analysis facilitated to locate highest and lowest potential regions in these molecules. Hydrogen atom abstraction property (radical scavenging property) of the molecules is studied with the help of hydrogen atom transfer mechanism.

Metabolite profile always hold important place for flavonoids as they are the major promoters of secondary metabolism in human body. For decades numerous flavonoids are explored for their structural activities which in turn helped them to meet various health promoting applications such as radical scavenging activity. Apart from conventional flavonoids their derivatives are also tend to exhibit similar kind of structural activity. Therefore, in the present work afzelin and juglanin – the glycosyl derivatives of kaemepferol an established flavonoid are subjected to structural activity relationship analysis using density functional theory. The structures of the two kaempferol glycosides are optimized and the optimized geometry is simulated to obtain frontier orbitals, electrostatic potential energy and molecular descriptors. The obtained results suggest that maximum amount of charge is accumulated over B-ring of two flavonoids, thus prefers to act as better electron donating region. Target predicted for two flavonoids over homosapien class reveal that the flavonoid highly prefers lyase and enzymatic targets for inhibition purpose.

A theoretical quantum study of the organophosphorus compound with formula C10H19OPCl2 (MEPCL2) was carried out. The results of the calculations show excellent agreement between experimental and computed frequencies evaluated at the B3LYP/6-311++G(d,p) level of theory. A study of the electronic properties, such as excitation energies and wavelengths were performed employing the time-dependent DFT (TD-DFT) method. Global a chemical reactivity of MEPCL2 was analyzed through global reactivity descriptors, while its local reactivity was analyzed by mean maps of the electrostatic potential. Also, the orbital energies values suggest that a charge transfer is occurring within the molecule.

The antioxidant power of eugenol and vitamin C was examined by analyzing the ability of these ligands to bind to the NADPH oxidase protein target and evaluating their bond interactions with critical residues. The results confirm that docked ligands are more stable in the specified active region of 2CDU during a MD simulation of 100 ns and 2CDU protein-ligand interactions with docked ligands showed significant hydrogen bond, hydrophobic, and water bridge formation. Eugenol exhibits hydrogen bond interactions with critical residues in the selective pocket in comparison to vitamin C. Also, eugenol had a similar binding orientation and very considerable stability in the selective pocket of 2CDU with a high binding energy with lipophilic energy. The electrostatic potential maps indicate that for eugenol, the –OH and –OCH3 sites, while that the –OH and –CO functional groups in vitamin C are responsible of the antioxidant activities of these compounds. HAT and SET mechanisms suggest that eugenol may become a better antioxidant than vitamin C.

In this work, a computational chemical study of Etoricoxib was carried out at the X/6311G(d,p) (where X=B3LYP, M06 and B97XD) level of theory, at the gas, aqueous and ethanol phases. Through the chemical reactivity descriptors derived from the DFT, it was possible to find that Etoricoxib structure exhibits a major chemical activity in water and ethanol phases in comparison to the gas phase, which suggests this drug would be more active in biological solvents like in blood, tissues and places where the ciclooxigenasa 2 (COX)-2 is found. In addition, a molecular docking analysis was conducted to study the interaction of Etoricoxib with the COX-2 active site. The results suggest that Etoricoxib interacts with 19 amino acid residues inside the COX-2 active site.

A bacterial biofilm is a cluster of bacterial cells embedded in a self-produced matrix of extracellular polymeric substances such as DNA, proteins, and polysaccharides. Several diseases have been reported to cause by bacterial biofilms, and difficulties in treating these infections are of concern. This work aimed to identify the inhibitor with the highest binding affinity for the receptor protein by screening various inhibitors obtained from Azorella species for a potential target to inhibit dispersin B. This work shows that azorellolide has the highest binding affinity (− 8.2 kcal/mol) among the compounds tested, followed by dyhydroazorellolide, mulinone A, and 7-acetoxy-mulin-9,12-diene which all had a binding affinity of − 8.0 kcal/mol. To the best of our knowledge, this is the first study to evaluate and contrast several diterpene compounds as antibacterial biofilm chemicals. Methods: Here, molecular modelling techniques tested 49 diterpene compounds of Azorella and six FDA-approved antibiotics medicines for antibiofilm activity. Since protein-like interactions are crucial in drug discovery, AutoDock Vina was initially employed to carry out structure-based virtual screening. The drug-likeness and ADMET properties of the chosen compounds were examined to assess the antibiofilm activity further. Lipinski’s rule of five was then applied to determine the antibiofilm activity. Then, molecular electrostatic potential was used to determine the relative polarity of a molecule using the Gaussian 09 package and GaussView 5.08. Following three replica molecular dynamic simulations (using the Schrodinger program, Desmond 2019-4 package) that each lasted 100 ns on the promising candidates, binding free energy was estimated using MM-GBSA. Structural visualisation was used to test the binding affinity of each compound to the crystal structure of dispersin B protein (PDB: 1YHT), a well-known antibiofilm compound.

A new amlodipine-chitosan nanocomposite was built using amlodipine nanoparticles as primary scaffolds by spontaneous emulsification, and its complete elucidation was performed by using several spectrometric techniques. Our results indicate that the amlodipine-chitosan nanocomposite has better solubility than amlodipine at pH 7.4 with a nearly all the drug substance dissolved (97%) by the final time-point measured. The docking study support the existence of intermolecular interactions are established between amlodipine and chitosan