Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: In silico and in vitro approach.

This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (10, 9, 4, and 7) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions.

Synergistic effects of essential oils and phenolic extracts on antimicrobial activities using blends of Artemisia campestris, Artemisia herba alba, and Citrus aurantium.

This study explores the synergistic antibacterial effects of essential oils (EOs) and phenolic extracts from three plants against foodborne pathogenic bacteria. The present work aimed to investigate the synergistic effects of the binary and the ternary combinations of extracts using different blend proportions of the following plant extracts: Artemisia campestris (AC), Artemisia herba alba (AHA), and Citrus aurantium (CA). The antimicrobial activities of EOs and phenolic extracts were determined and evaluated against five strains. For the EOs, the results of the DIZ showed the existence of synergism for different combinations of binary blends, such as AC/AHA or AHA/CA against Escherichia coli, and AC/CA against Enterobacter faecalis. In addition, ternary blends of AC:AHA:CA at a ratio of 1/6:2/3:1/6 exhibited a synergy effect, as measured by the CI, against E. coli. On the other hand, for the phenolic extracts, synergistic effects were noticed for binary blends of AC/CA at different ratios against E. coli, E. faecalis, and Pseudomonas aeruginosa strains. Similarly, ternary blends of phenolic extracts presented synergy against E. coli, E. faecalis, P. aeruginosa strains, and even C. albicans. In this case, the blending ratios were crucial determining factors for maximizing the synergy effect. The study established that the proportion of a single drug could play an essential role in determining the bioefficacy of a drug combination treatment. Therefore, the results showed the importance of studying the modulation of antibacterial activities based on the proportions of extracts in the mixture and finding the range of proportions (as determined by SLMD) that have a synergistic/additive/antagonistic effect with no or low side effects, which can be used in a food preservation system.

In vitro study of the antioxidant, sun factor protection, antimicrobial, and antifungal activities with molecular docking of methanolic extracts from leaves and fruit of Phillyrea angustifolia L.

This study aimed to evaluate the potential therapeutic effects of Phillyrea angustifolia L leaves and fruits from Algeria. The total phenolic and flavonoid contents, sun protection factor, antimicrobial, antifungal, and antioxidant activities such as DPPH, ABTS, FRAP, CUPRAC, and o-phenanthroline reduction were determined. The findings of the comparative analysis revealed that the leaves contained higher levels of total phenolic content (TPC) and flavonoid content (TFC) compared to the fruit, indicating their maximum antioxidant potential. TPC values for leaves ranged from 528.411 ± 9.94 to 816.352 ± 5.09 µg EAG/mg of dry extract, while for fruits, it ranged from 378.215 ± 5.26 to 579.392 ± 14.2 µg EAG/mg extract/ml. Similarly, TFC values for leaves varied from 65.833 ± 9.42 to 147.986 ± 5.59 µg EAG/mg of dry extract, and for fruits, it ranged from 45.486 ± 5.00 to 90.208 ± 6.77 µg EAG/mg extract/ml. Moreover, both leaves and fruit extracts showed significant growth inhibition against Staphylococcus aureus and Enterococcus faecalis, with the highest activity against Staphylococcus aureus, followed by Escherichia coli. The sun protection factor (SPF) values of both leaves and fruits extracts are close to the values of standard sunscreen VICHY. In addition, molecular docking studies identified promising compounds, including Demethyloleuropein, Luteolin-7-O-glucoside, Apigenin 7-Glucoside, Oleuropein, Pinoresinol, and Syringaresinol monoglucopyranoside of leaves from P. angustifolia L, these compounds are showing a better binding affinity than native ligands against Rhomboid protease GlpG from E. coli, the same thing about luteolin-7-O-glucoside and apigenin 7-glucoside exhibited similar binding free energy values to the target protein S. aureus sortase A. The study suggests that leaves and fruits of Phillyrea angustifolia L could be valuable sources for developing drugs against pathogenic oral yeasts, Gram-negative and Gram-positive bacteria. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03877-5.

Rosmarinus officinalis essential oils' eradication of beta-lactamase and multidrug resistant clinical bacterial pathogens from hospital settings.

Antibiotics have become increasingly ineffective in the face of bacterial resistance, particularly in hospitals. Interestingly, there is high demand for bioprospecting of secondary metabolites, particularly for treating multidrug-resistant clinical diseases. In fact, Rosemary has been used for its antiseptic properties dating back to antiquity. The aim of this research is to evaluate the effectiveness of Rosmarinus officinalis essential oil against multidrug-resistant clinical bacterial pathogens. Results showed promising antibacterial activity against seven bacteria: Escherichia coli, Enterobacter cloacae, Staphylococcus aureus, Serratia odorifera, Klebsiella pneumoniae, Klebsiella oxytoca, Aeromonas hydrophila with MIC values of 35.7, 17.85, 71.4, 8.9, 17.8, 285.7, 35.7 µg/ml respectively and MBC values of 142.8, 71.4, 285.7, 35.7, 71.4, 571.5,71.4 µg/ml respectively. This study suggests that Rosmarinus essential oil can be used as a therapeutic agent in the fight against a wide range of multi-resistant bacteria.

Geopolitical risk, economic policy uncertainty, and dynamic connectedness between clean energy, conventional energy, and food markets.

The global financial markets suffered unprecedented shocks, leading to significantly increased uncertainty in the markets due to various economic and financial recessions and geopolitical tensions, resulting in substantial fluctuations in market prices. Therefore, this paper aims to identify the response of the clean energy, conventional energy, and food markets to economic uncertainty and political tension while considering the influence of numerous crises and political conflicts. To achieve this, we employ the DCC-GARCH-based connectedness approach and the quantile-on-quantile model on monthly data spanning from May 2008 to June 2023. The results provide evidence of the sensitivity of dynamic volatility spillovers between financial assets to GEPU and GPR during major economic and financial crises and geopolitical events. Notably, this sensitivity increases significantly during the global financial crisis (GFC), the European debt crisis, Brexit, the US presidential election, the COVID-19 pandemic, and the Russian-Ukrainian war. However, the investigation of the tail dependence structure reveals that the relationship between uncertainties and total volatility connectedness across various market conditions appears to be asymmetric and heterogeneous. Our findings assist policymakers and green investors in designing the most effective policies to mitigate the impact of uncertainties on both conventional and green investments. This is achieved through insightful knowledge about the primary drivers of contagion among these indices, all while not compromising sustainability goals.

HPLC-DAD-MS Characterization, Antioxidant Activity, α-amylase Inhibition, Molecular Docking, and ADMET of Flavonoids from Fenugreek Seeds.

Fenugreek (Trigonella foenum-graecum) has a great beneficial health effect; it has been used in traditional medicine by many cultures. Likewise, the α-amylase inhibitors are potential compounds in the development of drugs for the treatment of diabetes. The beneficial health effects of fenugreek lead us to explore the chemical composition of the seeds and their antioxidant and α-amylase inhibition activities. The flavonoid extraction from fenugreek seeds was achieved with methanol through a Soxhlet apparatus. Then, the flavonoid glycosides were characterized using HPLC-DAD-ESI-MS analysis. The antioxidant capacity of fenugreek seed was measured using DPPH, FRAP, ABTS, and CUPRAC assays. Finally, the α-amylase inhibition activity was carried out using in vitro and in silico methods. The methanolic extract was found to contain high amounts of total phenolics (154.68 ± 1.50 µg GAE/mg E), flavonoids (37.69 ± 0.73 µg QE/mg E). The highest radical-scavenging ability was recorded for the methanolic extract against DPPH (IC50 = 556.6 ± 9.87 µg/mL), ABTS (IC50 = 593.62 ± 9.35 µg/mL). The ME had the best reducing power according to the CUPRAC (A 0.5 = 451.90 ± 9.07 µg/mL). The results indicate that the methanolic extracts of fenugreek seed best α-amylase inhibition activities IC50 = 653.52 ± 3.24 µg/mL. Twenty-seven flavonoids were detected, and all studied flavonoids selected have good affinity and stabilize very well in the pocket of α-amylase. The interactions between the studied flavonoids with α-amylase were investigated. The flavonoids from fenugreek seed present a good inhibitory effect against α-amylase, which is beneficial for the prevention of diabetes and its complications.

In silico analysis of identified molecules using LC-HR/MS of Cupressus sempervirens L. ethyl acetate fraction against three monkeypox virus targets.

Monkeypox virus is a viral disease transmitted to humans through contact with infected animals, such as monkeys and rodents, or through direct contact with the bodily fluids or lesions of infected humans. The aim of this study is to evaluate in silico the inhibition effect of eight Cupressus sempervirens L. ethyl acetate fraction identified molecules using LC-MS on three monkeypox targets such as the vaccinia virus thymidylate kinase (VTK), the viral profilin-like protein (VPP), and the viral RNA polymerase (VRP). The study consist of using molecular docking with AutoDock vina based on the lowest energy value in kcal/mol, pharmacokinetics prediction with pre-ADMET v2.0 server, and prediction of biological activity with the PASS server tool. The best complexes were subjected to molecular dynamics simulation (MD) study to confirm their stability using Desmond software. The used molecules were vitamin C, vanillic acid (Pol), Flav1 (Catechin), Flav2 (Epicatechin), Flav3 (Hyperoside), Flav4 (Luteolin), Flav5 (Taxifolin), and Flav6 (Quercetin). The results show that flavonoids are potent to VTK, VPP and effectively block the VRP channel with energy values ranging from -7.0 to -9.3 kcal/mol. Further, MD simulation supports Flav1 and, Flav2 for notable stability in the VTK binding pocket through hydrogen and hydrophobic interactions. PASS results predicted various biological activities with promising VTK and VRP inhibition activities. The studied molecules could constitute a safer alternative to current drugs, which often cause adverse side effects.Communicated by Ramaswamy H. Sarma.

The chemical profile and seasonal variation of the composition of the phenolic acids in different plant parts of Centaurea sp.

This study investigated the seasonal variation (over seven months) of phenolic acid (PHA) components in different parts of Centaurea sp. The primary objective was to determine the pattern of variation, while the secondary objective was to identify which month or growth stage provides a greater total PHA content or percentage of bioactive components. Different patterns of seasonal variations were highlighted for the different PHA components and their classes (hydroxybenzoic and -cinnamic acids) in different parts of the plant. The leaves exclusively provided the highest PHA contents, with maximum values reached in April (1368.06 µg/g). The major hydroxybenzoic acid derivatives (HBAs) identified in the leaves were vanillic acid (VaA) "154.18-374.06 µg/g" and protocatechuic acid (PA) "9.37-595.61 µg/g", while the major hydroxycinnamic acid derivatives (HCAs) were p-coumaric acid (p-CoA) "109.35-261.77 µg/g", m-coumaric acid (m-CoA) "10.22-70.57 µg/g", and ferulic acid (FeA) "35.54-109.13 µg/g". The maximum percentage of PA was obtained in April "595.61 µg/g", while the maximum p-CoA content was obtained in January "261.77 µg/g". Therefore, the leaves can be recommended as the optimal source of PHAs. If there is a specific interest in certain PHA components, we recommend collection in either January or April. Multivariate statistical analysis (PCA & AHC) showed the existence of two main clusters. The first cluster comprised the leaves, distinguished by the highest VaA, PA, and p-CoA contents. The second cluster comprised roots and the root bark samples. This study provides information on the development of PHAs in different parts of Centaurea sp. and explores potential applications. It will be of considerable interest for determining the optimal harvesting time of shrub species used for their medicinal properties and bio-active phenolic contents.

Revisiting the relationship between business conditions, climate policy uncertainty, and environmental pollution: evidence from the USA.

This paper aims to revisit the interdependency between business conditions, climate policy change, and the environmental pollution of the USA. Interestingly, our paper represents a completion to the existing literature on three levels at least. First, we propose to analyze this issue during normal periods and periods of turmoil, particularly the COVID-19 outbreak. To do so, contrary to previous studies that used economic growth, we employ the ADS index as a real-time business conditions measurement. Second, we employ a frequency approach, based on the continuous wavelet transform, allowing us to understand the nature of the relationship. Understanding whether the relationship holds in the short- or long-term is useful for policymakers in monitoring public policies to achieve CO2 emission reduction as well as to investors interested in high value-added projects. Our analysis shows that, during the last two decades, the relationship between business conditions as well as climate uncertainty index and CO2 emissions is observed during the long- and short-term, and driven through economic conditions. However, during the crisis periods, the effect is detected across various scales and the relationship is bi-directional. Our results have several practical implications for the US policymakers to consider when setting policies for fighting pollution emissions and environmental protection.

What can we learn about the market reaction to macroeconomic surprise? Evidence from the COVID-19 crisis.

We investigate the impact of macroeconomic surprise and uncertainty on G7 financial markets around COVID-19 pandemic using two real-time, real-activity indexes recently constructed by Scotti (2016). We applies the wavelet analysis to detect the response of the stock markets to the macroeconomic surprise and an uncertainty indexes and then we use NARDL model to examine the asymmetric effect of the news surprise and uncertainty on the equity markets. We conduct our empirical analysis with the daily data from January, 2014 to September, 2020. Our findings indicate that G7 stock markets are sensitive to the macroeconomic surprise and uncertainty and the effect is more pronounced at the long term than the short term. Moreover, we show that the COVID-19 crisis supports the relationship between the macroeconomic indexes and the stock prices. The results are useful for investment decision-making for the investors on the G7 stock indices at different investment horizons.

Mineral Profile, Antioxidant, Anti-Inflammatory, Antibacterial, Anti-Urease and Anti-α-Amylase Activities of the Unripe Fruit Extracts of Pistacia atlantica.

Pistacia Atlantica in folk medicine is used by Algerian traditional healers for treating a wide variety of diseases and conditions including dyspepsia, digestive problems, peptic ulcers, and, in particular, inflammatory diseases. The present study aimed to assess the phytochemical composition, in vitro antioxidant activity (using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ABTS+, and reducing power methods), enzyme inhibitory activity (towards α-amylase and urease), antibacterial activity, and in vivo anti-inflammatory activity of the unripe fruit extracts of Pistacia atlantica collected from different parts of the Djelfa region of Algeria. According to the findings, various aqueous extracts exhibited significant antioxidant and enzymatic activities in all tests, but showed that they have a weak inhibitory effect against all tested bacterial strains. Twenty-one minerals comprising both macro- and microelements (Ba, Br, Ca, Cl, Co, Cr, Cs, Eu, Fe, K, Mg, Mn, Mo, Na, Rb, Sb, Sc, Sr, Th, U, and Zn) were determined using the technique of neutron activation analysis (INAA). The result indicates that the concentration of the mineral element is close to the minimal FAO recommendation. In addition, the result revealed significant anti-inflammatory activities. The data generated can be a valuable source of information for the pharmaceutical industry and medical research. These results suggest that the unripe fruit extracts of Pistacia atlantica have an appropriate potential to be utilized across a wide range of contexts as an agent with multifunctional uses, as well as a natural remedy for other physiological diseases.

Hydroxycoumarins and some Flavonoids from Pistacia atlantica Desf. as Multi-targets Inhibitors for Alzheimer's Disease: Molecular Docking and ADMET Studies.

OBJECTIVE: The present study aimed to identify new selective inhibitors for acetylcholinesterase, butyrylcholinesterase, monoacylglycerol lipase, beta-secretase, and Asparagine endopeptidase, the targets enzymes in Alzheimer's disease. METHODS: The inhibitory effect of P. atlantica Desf. methanol extracts against AChE were determined using Ellman's method. The molecular docking study is achieved using Autodock Vina. The structures of the molecules 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7- trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside and the five enzymes were obtained from the PubChem database and Protein databank. ADMET parameters were checked to confirm their pharmacokinetics using swiss-ADME and ADMET-SAR servers. RESULTS: P. atlantica Desf. methanol extracts showed a notable inhibitory effect against AChE (IC50 = 0.26 ± 0.004 mg/ml). The molecular docking results of 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7-trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-Orutinoside with the five enzymes show significant affinities of these molecules towards Alzheimer disease targets, where they could form several interactions, such as hydrogen bonds and hydrophobic interactions with the studied enzymes. The shortest hydrogen bond is 1.7 A° between masticadienonic acid and Arg128 of the active site of BACE, while the lowest free energy is -11.2 of the complex 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside -HuBchE. To the best of our knowledge, these molecules' potential anti-Alzheimer disease effect is studied in this paper for the first time. CONCLUSION: The docking studies of this work show that 3-methoxycarpachromene and masticadienonic acid, 7-ethoxycoumarin, 3',5,7-Trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol- 3-O-rutinoside have good affinities towards the enzymes involved in Alzheimer pathology, which confirm the ability of these molecules to inhibit the studied enzymes namely: HuAChE, HuBChE, BACE, MAGL, and AEP. These molecules might become drug candidates to prevent Alzheimer's disease.

In vitro oxidation of hispidin and gallic acid by horseradish peroxidase.

Gallic acid and hispidin have been previously described by us as inhibitors of horseradish peroxidase (Benarous, K., Benali, F. Z., Bekhaoua, I. C., and Yousfi, M. Journal of Biomolecular Structure & Dynamics, (2021) 39(18), 7168-7180). However, additional experiments have demonstrated that under the applied assay conditions both compounds are rapidly oxidized by this enzyme. After oxidation, the components of the reaction mixture undergo complex reactions giving products with much weaker absorption at the detection wavelength. This was interpreted by us as enzyme inhibition, which, however, is only apparent. In fact, the activity of horseradish peroxidase is not affected by these compounds, which was demonstrated by measurements of hydrogen peroxide consumption.Communicated by Ramaswamy H. Sarma.

Cupressus sempervirens L. flavonoids as potent inhibitors to xanthine oxidase: in vitro, molecular docking, ADMET and PASS studies.

Excessive intake of purine-rich foods such as seafood and red meat leads to excess xanthine oxidase activity and provokes gout attacks. The aim of this paper is to evaluate in vitro and in silico, the inhibition effect of Cupressus sempervirens plant extracts (flavonoids (Cae) and alkaloids (CaK)) and its six derivative compounds on bovine xanthine oxidase (BXO). The in silico study consists of molecular docking with GOLD v4.0 based on the best PLPchem score (PLP) and prediction of biological activity with the PASS server tool. The inhibitors used were lignan (cp1), Amentoflavone (cp2), Cupressuflavone (cp3), Isocryptomerin (cp4), Hinokiflavone (cp5), and Neolignan (cp6). The in vitro results showed that CaK gives an IC50 of 3.52 ± 0.04 µg/ml. Similarly, Cae saved an IC50 of 8.46 ± 1.98 µg/ml compared with the control (2.82 ± 0.10 µg/ml). The in silico results show that cp1 was the best inhibitor model (PLP of 88.09) with approved pharmacokinetics. These findings suggest that cp1 and cp2 may offer good alternatives for the treatment of hyperuricemia; cp3 was moderate, while the others (cp4 to cp6) were considered weak inhibitors according to their PLP.Communicated by Ramaswamy H. Sarma.

Development and Characterization of Phosphate Glass Fibers and Their Application in the Reinforcement of Polyester Matrix Composites.

This study focused on the production and characterization of phosphate glass fibers (PGF) for application as composite reinforcement. Phosphate glasses belonging to the system 52P2O524CaO13MgO (11-(X + Y)) K2OXFe2O3YTiO2 (X:1, 3, 5) and (Y:0.5, 1) were elaborated and converted to phosphate glass fibers. First, their mechanical properties and chemical durability were investigated. Then, the optimized PGF compositions were used afterward as reinforcement for thermosetting composite materials. Polyester matrices reinforced with short phosphate glass fibers (sPGF) up to 20 wt % were manufactured by the contact molding process. The mechanical and morphological properties of different sPGF-reinforced polyester systems were evaluated. The choice between the different phosphate-based glass syntheses (PGFs) was determined by their superior mechanical performance, their interesting chemical durability, and their high level of dispersion in the polyester matrix without any ad sizing as proven by SEM morphological analysis. Moreover, the characterization of mechanical properties revealed that the tensile and flexural moduli of the developed polyester-based composites were improved by increasing the sPGF content in the polymer matrix in perfect agreement with Takayanagi model predictions. The present work thus highlights some promising results to obtain high-quality phosphate glass fiber-reinforced polyester parts which can be transposed to other thermosetting or thermoplastic-based composites for high-value applications.

Recent Advances in the Interfacial Shear and Dilational Rheology of Polymer Systems: From Fundamentals to Applications.

The study of the viscoelastic properties of polymer systems containing huge internal two-dimensional interfacial areas, such as blends, foams and multilayer films, is of growing interest and plays a significant role in a variety of industrial fields. Hence, interfacial rheology can represent a powerful tool to directly investigate these complex polymer-polymer interfaces. First, the current review summarizes the theoretical basics and fundamentals of interfacial shear rheology. Particular attention has been devoted to the double-wall ring (DWR), bicone, Du Noüy ring and oscillating needle (ISR) systems. The measurement of surface and interfacial rheological properties requires a consideration of the relative contributions of the surface stress arising from the bulk sub-phases. Here, the experimental procedures and methodologies used to correct the numerical data are described considering the viscoelastic nature of the interface. Second, the interfacial dilational rheology is discussed, starting with the theory and underlying principles. In particular, the Langmuir trough method, the oscillating spinning drop technique and the oscillating pendant drop technique are investigated. The major pioneering studies and latest innovations dedicated to interfacial rheology in both shear and dilatation-compression are highlighted. Finally, the major challenges and limits related to the development of high-temperature interfacial rheology at the molten state are presented. The latter shows great potential for assessing the interfaces of polymer systems encountered in many high-value applications.

COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. METHODS: We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. RESULTS: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). CONCLUSION: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

Quinic and Digallic acids from Pistacia atlantica Desf. Leaves Extracts as Potent Dual Effect Inhibitors against main Protease and RNA-dependent RNA Polymerase of SARS-CoV-2.

BACKGROUND: Through this study, the Chemical composition realized by UHPLC-DADESI- MSn allowed the detection of different phenolic compound groups from Pistacia atlantica Desf. leaves extracts. We studied the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 by the identified molecules through molecular docking. OBJECTIVE: The objective of this study is to identify compounds from Pistacia atlantica Desf. leaves extracts, which might have anti-viral effects. METHODS: Chemical composition was realized by UHPLC-DAD-ESI-MSn, and the inhibition of the main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 was studied using molecular docking with Autodock Vina software. ADMET analysis was carried out. RESULTS: The identified compounds are quinic acid, digallic acid, galloylquinic acid, gallic acid, trigallic acid, digalloylquinic acids, trigalloylquinic acids and methyl gallate; digallic and quinic acids are the best inhibitors. Digallic acid had binding affinity energy (BAE) of -8.2 kcal/mol, and Ki of 1µM for the CL3 Mpro, Ki of 0.62 mM for the RdRp. Quinic acid showed Ki of 4.6 mM, recorded for both enzymes. Through ADMET analysis, we have found that the two molecules are good drug candidates. CONCLUSION: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves are studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.

Outbreak of Imported Seventh Pandemic Vibrio cholerae O1 El Tor, Algeria, 2018.

After a lull of >20 years, Algeria experienced a cholera outbreak in 2018 that included 291 suspected cases. We found that outbreak isolates were Vibrio cholerae O1 serotype Ogawa from seventh pandemic El Tor sublineage AFR14, which corresponds to a new introduction of cholera into Africa from South Asia.

The inhibitory kinetics of vitamins B9, C, E, and D3 on bovine xanthine oxidase: Gout treatment.

BACKGROUND: Over-consumption of foods high in purines like seafood, red meat, and alcoholic beverages leads to hyperuricemia causing gout attacks. Xanthine oxidase was reported responsible for the overproduction of uric acid. MATERIAL AND METHODS: We intend to test in silico and in vitro, the inhibition effect of four vitamins against bovine milk xanthine oxidase (BXO). We performed Molecular docking with GOLD v4.0, and the biological activity prediction with the PASS server. The best-selected vitamins were chosen based on their best PLPchem score. The BXO constant Km and Vmax were determined in vitro, and then the vitamins were tested for their inhibition effect to BXO. Furthermore, the inhibition constant Ki of each inhibitor were determined using Dixon method, the vitamins chosen were vitamin E, vitamin B9, vitamin D3, and vitamin C. RESULTS: The in silico results show that the tested vitamins were the best inhibitors model with PLPchem scores up to 70 comparing to the control. The in vitro results show that BXO have a Km value of 163.55 µM with Vmax of 37 U, vitamins B9, E, C, and D3 were potent inhibitors to BXO with an IC50 of 34.10 ± 0.21, 36.68 ± 1.50, 39.01 ± 0.02, and 100.28 ± 0.33 µM, respectively comparing to the control (32.03 ± 0.73 µM). The kinetic study shows that all tested vitamins were Non-competitive inhibitors, the Ki values were 15 ± 1.76 µM, 29 ± 1.06 µM, 12 ± 1.41 µM, and 20 ± 0.71 µM, for respectively vitamins B9, E, C, and D3. CONCLUSION: The obtained results promise an excellent strategy using vitamins to enhance immunity, treat hyperuricemia, and minimize the usual drug side effects.