Bilastine Based Drugs as SARS-CoV-2 Protease Inhibitors: Molecular Docking, Dynamics, and ADMET Related Studies

Bilastine drugs, structurally piperidine-1-carboxylate and sulfonyloxyethyl carboxylate derivatives, have significantly been employed as the medication of second-generation antihistamine drugs, and are used for the treatment of allergic rhinoconjunctivities and urticarial (hives). The bilastine drugs, composed of benzene carboxylate, propanoate, carboxylate, methyl-sulfonate, propanoic acid, butanoic acid, and pentanoic acid derivatives, were investigated through computational tools against SARS-CoV-2. The COVID-19 virus consists of five proteases where the curial function is performed by main proteases (Mpro) and Spike proteases (Spro). The Mpro and Spro were selected for calculation of molecular docking by these bilastine drugs which showed higher binding energy (<-6.5 kcal/mol) for both proteases. The main carboxylic acid group in bilastine drugs is found the primary key for a high binding score to show the large binding affinity with Mpro and Spro, and is highly responsible for forming the hydrogen bond although the various hydrophobic bonds were produced as a weak interaction. For justification, the stability of molecular docked ligand-protein complexes was investigated with molecular dynamics. It showed that the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of all these drugs were below the 0.9 Å after residue interaction. Moreover, the HOMO-LUMO gap, hardness, and softness provided full details for their chemical reactivity. In this view, the pharmacokinetics and Lipinski rule were calculated, and all of these molecules had satisfied the Lipinski rule. Finally, using the admetSAR online database, absorption, distribution, metabolism, excretion, and toxicity have been calculated which indicated that these bilastine drugs are non-carcinogenic and less harmful for both aquatic and non-aquatic species. DOI: http://dx.doi.org/10.17807/orbital.v14i1.164

The Effects of Oxidation States, Spin States and Solvents on Molecular Structure, Stability and Spectroscopic Properties of Fe-Catechol Complexes: A Theoretical Study

In this study, in order to explain the solvent and spin state effects on the molecular structure of catechol-Fe complex [Fe(cat)3]n﹣ where n = 2 and 3, Hartree Fock (HF)-Density Functional Theory (DFT) hybrid calculations are performed at the B3LYP/6-311g(d,p) level of theory. The binding energies of Fe2+ and Fe3+ in high-spin state are higher than intermediate and low-spin states which show that the complex formation in a high spin state is more favorable. The calculated binding energies at different solvents indicate that the binding energies in polar solvents are lower than non-polar solvents. Furthermore, spectroscopic studies including FTIR and Raman spectrum in various solvents reveal that the formation of intermolecular bonds between the oxygen atom of carbonyl group and the hydrogen atom of solvent causes a spectral red shift. The calculated FTIR and geometry parameters are in good agreement with previous experimental data. Donor-acceptor interaction energies are evaluated due to the importance of the charge transfer in the complex formation. It is observed that the free electrons of oxygen atom interact with the antibonding orbitals of the iron. Finally, some correlations between the quantum chemical reactivity indices of the complexes and solvent polarity are considered. The study indicates a linear correlation between chemical hardness and binding energies of [Fe(cat)3]3﹣ complex.Regional Scientific Computing Center for Lower Saxony (RRZN

Synthesis, Antimicrobial, and DFT Studies of Some Benzyl 4-O-Acyl-α-L-rhamnopyranosides

Application of carbohydrate fatty acid (CFA) esters in food and beverage industries has increased their interest in other fields. Especially rhamnopyranoside esters having both the hydrophilic and lipophilic nature had broader applications including anticancer activities. Benzyl α-L-rhamnopyranoside, prepared from L-rhamnose, on 2,3-O-isopropylidene protection with 2,2-dimethoxypropane followed by acylation at C-4 hydroxyl position with different acylating agents furnished the corresponding 4-O-acyl-α-L-rhamnopyranosides in good yields. All the compounds were well characterized by spectroscopic techniques. In vitro antimicrobial activities against eight bacterial and two fungal pathogens indicated that these 2,3-O-isopropylidene protected rhamnopyranosides had weak to moderate inhibitory properties. To rationalize such moderate activities structural (conformational) distortion of these monoacetonide protected CFA esters were studied from the density functional theory (DFT) optimized structures. In addition, thermodynamic properties including frontier molecular orbitals of the synthesized rhamnopyranosides were calculated and discussed. Corroboration of all the studies signifies that the moderate antimicrobial efficacy of the isopropylidene protected rhamnopyranosides might be due to their distorted conformations, lower softness and smaller dipole moments. DOI: http://dx.doi.org/10.17807/orbital.v13i3.161

Bilastine Based Drugs as SARS-CoV-2 Protease Inhibitors: Molecular Docking, Dynamics, and ADMET Related Studies

Bilastine drugs, structurally piperidine-1-carboxylate and sulfonyloxyethyl carboxylate derivatives, have significantly been employed as the medication of second-generation antihistamine drugs, and are used for the treatment of allergic rhinoconjunctivities and urticarial (hives). The bilastine drugs, composed of benzene carboxylate, propanoate, carboxylate, methyl-sulfonate, propanoic acid, butanoic acid, and pentanoic acid derivatives, were investigated through computational tools against SARS-CoV-2. The COVID-19 virus consists of five proteases where the curial function is performed by main proteases (Mpro) and Spike proteases (Spro). The Mpro and Spro were selected for calculation of molecular docking by these bilastine drugs which showed higher binding energy (<-6.5 kcal/mol) for both proteases. The main carboxylic acid group in bilastine drugs is found the primary key for a high binding score to show the large binding affinity with Mpro and Spro, and is highly responsible for forming the hydrogen bond although the various hydrophobic bonds were produced as a weak interaction. For justification, the stability of molecular docked ligand-protein complexes was investigated with molecular dynamics. It showed that the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of all these drugs were below the 0.9 Å after residue interaction. Moreover, the HOMO-LUMO gap, hardness, and softness provided full details for their chemical reactivity. In this view, the pharmacokinetics and Lipinski rule were calculated, and all of these molecules had satisfied the Lipinski rule. Finally, using the admetSAR online database, absorption, distribution, metabolism, excretion, and toxicity have been calculated which indicated that these bilastine drugs are non-carcinogenic and less harmful for both aquatic and non-aquatic species. DOI: http://dx.doi.org/10.17807/orbital.v14i1.164

The effects of protecting and acyl groups on the conformation of benzyl α-Lrhamnopyranosides: An in silico study

Carbohydrate fatty acid (CFA) esters especially rhamnopyranoside esters having both the hydrophilic and lipophilic nature showed broader applications including anticancer activities. It was reported that appropriate conformation is needed for better activities and conformational distortion reduced antimicrobial functionality. In this context, two different esters series of benzyl α-L-rhamnopyranosides, one with 2,3-O-acetonide group and the other one without acetonide group, were subjected for the density functional theory (DFT) optimization. The optimized structures with 2,3-O-acetonide rhamnopyranoside clearly showed distortion from the regular 1C4 chair conformation while rhamnopyranoside esters without 2,3-O-acetonide functionality exhibited almost regular 1C4 chair conformation. Also, the number and position of acyl group(s) present in the benzyl rhamnopyranoside imposes a small effect on their pyranose chair conformation. Thermodynamic properties including frontier molecular orbitals (FMO) and molecular electrostatic potential (MEP) of both the series of rhamnopyranosides are also discussed which indicated that 4-O-acyl rhamnopyranosides are more reactive than the 3-O-acyl analogues

Comparative Antibacterial Activities of Some Monosaccharide and Disaccharide Benzoates

For comparative antibacterial studies a number of furanose (3, 5), pyranose (7, 9, 11, 13), and disaccharide benzoates (14, 15) were prepared by direct benzoylation method. Synthesized benzoates (3, 5, 7, 9, 11, 13-15) along with some starting materials were screened for in vitro antibacterial activity against ten human pathogenic bacteria viz. Bacillus subtilis, Bacillus cereus, Bacillus megaterium, Staphylococcus aureus, Escherichia coli, INABA ET (Vibrio), Pseudomonas species, Salmonella paratyphi, Salmonella typhi, and Shigella dysenteriae. The study revealed that the pyranose benzoate derivatives (7, 9, 11, 13) were more prone towards antibacterial functionality than that of the furanose benzoate (3, 5) and disaccharide benzoates (14, 15). DOI: http://dx.doi.org/10.17807/orbital.v7i2.69

Plant Based Polyphenol Associations with Protein : A Prospective Review

This review discusses the classes of plant polyphenols along with their binding mechanisms with protein molecules. Generally, polyphenols bind in covalent and non-covalent orientations with protein molecules. Their addition to the protein usually results in undesirable flavors and tastes inside the proteins. They also affect the color of the food. Plant polyphenols are found to act in a protective way against cardiovascular disease, neurodegenerative diseases, diabetes, and cancer. In addition to redox activity, their modes of action include the inhibition of key enzymes, modulation of transcription factors or cell receptors, and finally, perturbation of protein aggregates. Dietary polyphenols usually play a key role in protein digestion by forming covalent and non-covalent bonds with proteins. In addition, polyphenols and plant phenolics possess the scavenging ability of reactive oxygen species (ROS), including radical/non-radical oxygen species including HOC•, H2O2, HOCl, 1O2 (singlet oxygen), and oxidatively generated radicals derived from LDL biomolecules such as ROOC• and oligonucleic acids

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0.71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50.2% exceed this threshold for suitability in at least one 5×5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify

Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3

Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available