In silico prediction of potential inhibitors for SARS-CoV-2 Omicron variant using molecular docking and dynamics simulation-based drug repurposing.

BACKGROUND: In November 2021, variant B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified by the World Health Organization (WHO) and designated Omicron. Omicron is characterized by a high number of mutations, thirty-two in total, making it more transmissible than the original virus. More than half of those mutations were found in the receptor-binding domain (RBD) that directly interacts with human angiotensin-converting enzyme 2 (ACE2). This study aimed to discover potent drugs against Omicron, which were previously repurposed for coronavirus disease 2019 (COVID-19). All repurposed anti-COVID-19 drugs were compiled from previous studies and tested against the RBD of SARS-CoV-2 Omicron. METHODS: As a preliminary step, a molecular docking study was performed to investigate the potency of seventy-one compounds from four classes of inhibitors. The molecular characteristics of the best-performing five compounds were predicted by estimating the drug-likeness and drug score. Molecular dynamics simulations (MD) over 100 ns were performed to inspect the relative stability of the best compound within the Omicron receptor-binding site. RESULTS: The current findings point out the crucial roles of Q493R, G496S, Q498R, N501Y, and Y505H in the RBD region of SARS-CoV-2 Omicron. Raltegravir, hesperidin, pyronaridine, and difloxacin achieved the highest drug scores compared with the other compounds in the four classes, with values of 81%, 57%, 18%, and 71%, respectively. The calculated results showed that raltegravir and hesperidin had high binding affinities and stabilities to Omicron with ΔGbinding of - 75.7304 ± 0.98324 and - 42.693536 ± 0.979056 kJ/mol, respectively. Further clinical studies should be performed for the two best compounds from this study.

Highly Efficient Elimination of Pb+2 and Al+3 Metal Ions from Wastewater Using Graphene Oxide/3,5-Diaminobenzoic Acid Composites: Selective Removal of Pb2+ from Real Industrial Wastewater.

In this study, graphene oxide (GO) was functionalized with 3,5-diaminobenzoic acid (DABA) by a one-step method to produce functionalized graphene oxide (FGO). FGO is a new type of absorbent crystalline substance that has a high surface area and a large porosity site as well as a large number of dentate functional groups which lead to enhanced adsorption performance for heavy metal ions. The adsorption efficiency of FGO for Pb+2 and Al+3 metal ions was extra satisfactory when compared with GO due to the ease of design and the homogeneous structure of FGO. The structure of synthesized GO and FGO was confirmed by different techniques such as FTIR, XRD, TGA, BET nitrogen adsorption-desorption methods, and TEM analyses. The mass of utilized adsorbents, the pH of the medium, the concentration of ionic species in the medium, temperature, and process time were all investigated as variables in the adsorbent procedure. The experimental data recorded that the maximum adsorption efficiency of the 0.5 g/L FGO composite was 99.7 and 99.8% for Pb+2 and Al+3 metal ions, respectively, while in the case of using GO, the maximum adsorption efficiency was 92.6 and 91.9% at ambient temperature in a semineutral medium at pH 6 after 4 h. The adsorption results were in good conformity with the Freundlich model and pseudo-second-order kinetics for Pb+2 and Al+3 metal ions. Also, the reusability study indicates that FGO can be used repeatedly at least for five cycles with a slight significant loss in its efficiency.

Growth Inhibition of Sulfate-Reducing Bacteria during Gas and Oil Production Using Novel Schiff Base Diquaternary Biocides: Synthesis, Antimicrobial, and Toxicological Assessment.

Upstream crude oil production equipment is always exposed to destruction damagingly which is caused by sulfate-reducing bacterium (SRB) activities that produce H2S gas, which leads to increased metal corrosion (bio-fouling) rates and inflicts effective infrastructure damage. Hence, oil and gas reservoirs must be injected with biocides and inhibitors which still offer the foremost protection against harmful microbial activity. However, because of the economic and environmental risks associated with biocides, the oil and gas sectors improve better methods for their usage. This work describes the synthesis and evaluation of the biological activities as the cytotoxicity and antimicrobial properties of a series of diquaternary cationic biocides that were studied during the inhibition of microbial biofilms. The prepared diquaternary compound was synthesized by coupling vanillin and 4-aminoantipyrene to achieve the corresponding Schiff base, followed by a quaternization reaction using 1,6-bromohexane, 1,8-bromooctane, and 1,12-bromododecane. The increase of their alkyl chain length from 6 to 12 methylene groups increased the obtained antimicrobial activity and cytotoxicity. Antimicrobial efficacies of Q1-3 against various biofilm-forming microorganisms, including bacteria and fungi, were examined utilizing the diameter of inhibition zone procedures. The results revealed that cytotoxic efficacies of Q1-3 were significantly associated mainly with maximum surface excess and interfacial characteristics. The cytotoxic efficiencies of Q1-3 biocides demonstrated promising results due to their comparatively higher efficacies against SRB. Q3 exhibited the highest cytotoxic biocide against the gram +ve, gram -ve, and SRB species according to the inhibition zone diameter test. The toxicity of the studied microorganisms depended on the nature and type of the target microorganism and the hydrophobicity of the biocide molecules. Cytotoxicity assessment and antimicrobial activity displayed increased activity by the increase in their alkyl chain length.

Targeting Natural Plant Metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular Docking, Molecular Dynamics, and Physicochemical Properties Study.

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than -9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of -49.02, -48.07, and -67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.

Identification of promising anti-EBOV inhibitors: de novo drug design, molecular docking and molecular dynamics studies.

The Ebola virus (EBOV) outbreak was recorded as the largest in history and caused many fatalities. As seen in previous studies, drug repurposing and database filtration were the two major pathways to searching for potent compounds against EBOV. In this study, a deep learning (DL) approach via the LigDream tool was employed to obtain novel and effective anti-EBOV inhibitors. Based on the galidesivir (BCX4430) chemical structure, 100 compounds were collected and inspected using various in silico approaches. Results from the molecular docking study indicated that mol1_069 and mol1_092 were the best two potent compounds with a docking score of -7.1 kcal mol-1 and -7.0 kcal mol-1, respectively. Molecular dynamics simulations, in addition to binding energy calculations, were conducted over 100 ns. Both compounds exhibited lower binding energies than BCX4430. Furthermore, compared with BCX4430 (%Absorption = 60.6%), mol1_069 and mol1_092 scored higher values of % Absorption equal to 68.1% and 63.7%, respectively. The current data point to the importance of using DL in the drug design process instead of conventional methods such as drug repurposing or database filtration. In conclusion, mol1_069 and mol1_092 are promising anti-EBOV drug candidates that require further in vitro and in vivo investigations.

Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach.

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

Effect of Reaction Parameters on Catalytic Pyrolysis of Waste Cooking Oil for Production of Sustainable Biodiesel and Biojet by Functionalized Montmorillonite/Chitosan Nanocomposites.

The use of waste oils as pyrolysis feedstocks to manufacture high-grade biofuels has prompted researchers to focus on developing renewable energy to overcome the depletion of fossil fuel supplies and the global warming phenomena. Because of their high hydrogen and volatile matter concentration, waste oils are ideal raw materials for the production of biofuels. It is challenging to attain satisfactory results with conventional methods, such as transesterification, gasification, solvent extraction, and hydrotreating due to flaws such as high energy demand, long time, and high operating costs. Catalytic pyrolysis of waste edible oils was employed as a resource for the generation of biodiesel. The application of the catalytic cracking process has the potential to alleviate the existing situation. In this study of catalytic cracking conversion of waste cooking oil to produce different biofuels, grades were investigated using two heterogeneous catalysts. The catalysts were activated montmorillonite (PAMMT) clay and its modified form using a chitosan biopolymer (PAMMT-CH) nanocomposite. The catalysts were identified using infrared spectroscopy, X-ray diffraction patterns, transmittance electron microscopy images, surface area, and thermal stability. The catalysts were tested for their performances using different amounts (0.1-1% by weight) at a temperature assortment of 200-400 °C during a time range of 60-300 min. The experimental studies were carried out in a batch reactor. GC mass spectra were used to investigate the catalytic cracking products. Fractional distillation is used to separate the final products from various reaction conditions. The physicochemical properties of resulting biofuels were profiled by quantifying their densities, viscosities, specific gravities, pour points, flash and fire points, cetane numbers, carbon and ash residues, and sulfur contents. The optimum conditions of the yield product were 300 and 400 °C, catalyst weights of 0.7 and 0.8% w/v, and reaction times of 120 and 180 min concerning the (PAMMT) and (PAMMT-CH) nanocomposite, respectively. The determined properties were located within the limits of the specific standards of ASTM specifications. As a result, the PAMMT nanocomposite produced biofuel comparable to biodiesel according to ASTM specifications, while the PAMMT-CH nanocomposite produced biofuel comparable to biojet.

Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study.

Coronavirus disease 2019 (COVID-19) is a new pandemic characterized by quick spreading and illness of the respiratory system. To date, there is no specific therapy for Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Flavonoids, especially rutin, have attracted considerable interest as a prospective SARS-CoV-2 main protease (Mpro) inhibitor. In this study, a database containing 2017 flavone analogs was prepared and screened against SARS-CoV-2 Mpro using the molecular docking technique. According to the results, 371 flavone analogs exhibited good potency towards Mpro with docking scores less than -9.0 kcal/mol. Molecular dynamics (MD) simulations, followed by molecular mechanics-generalized Born surface area (MM/GBSA) binding energy calculations, were performed for the top potent analogs in complex with Mpro. Compared to rutin, PubChem-129-716-607 and PubChem-885-071-27 showed better binding affinities against SARS-CoV-2 Mpro over 150 ns MD course with ΔGbinding values of -69.0 and -68.1 kcal/mol, respectively. Structural and energetic analyses demonstrated high stability of the identified analogs inside the SARS-CoV-2 Mpro active site over 150 ns MD simulations. The oral bioavailabilities of probable SARS-CoV-2 Mpro inhibitors were underpinned using drug-likeness parameters. A comparison of the binding affinities demonstrated that the MM/GBSA binding energies of the identified flavone analogs were approximately three and two times less than those of lopinavir and baicalein, respectively. In conclusion, PubChem-129-716-607 and PubChem-885-071-27 are promising anti-COVID-19 drug candidates that warrant further clinical investigations.

Performance of chitosan polymer as platform during sensors fabrication and sensing applications.

Chitosan is an important polymer produced from deacetylation of several sea and insects crusts. Due to its environmental fate and biological biocompatibility, it can be used in several biological and environmental applications. Sensing of biological compounds in human bodies and also in serum, blood, and different body fluids has found an important application instead of direct determination of the body fluids using complicated tools. Sensing process of biological compounds during bio-analysis of the biological systems, especially human fluids lack of several parameters including: high sensitivity, repeatability, speed of analysis and biocompatibility of the used analytical methods, especially in-vivo analysis. That was due to the time between sample handling and sample determination can change various components and concentrations of the bio-compounds. The need for in-situ analysis was directed the researchers for biosensors to overcome the upgrading problems of bio-analysis. Biosensors were the future of this issue. Chitosan can reserve as great platform for fabrication of different sensors to determine the elements, compounds and body bioactive compounds. The presence of different terminal amino and hydroxyl groups within chitosan framework facilitates the immobilization of different biomarkers to be used as sensing elements for the determined compounds. The use of chitosan as sensors platform was enhanced by using chitosan in its nanoforms.