Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study

The COVID-19 outbreak continues to spread worldwide at a rapid rate. Currently, the absence of any effective antiviral treatment is the major concern for the global population. The reports of the occurrence of various point mutations within the important therapeutic target protein of SARS-CoV-2 has elevated the problem. The SARS-CoV-2 main protease (Mpro) is a major therapeutic target for new antiviral designs. In this study, the efficacy of PF-00835231 was investigated (a Mpro inhibitor under clinical trials) against the Mpro and their reported mutants. Various in silico approaches were used to investigate and compare the efficacy of PF-00835231 and five drugs previously documented to inhibit the Mpro. Our study shows that PF-00835231 is not only effective against the wild type but demonstrates a high affinity against the studied mutants as well.     

Fiber-optic beam shaper based on multimode interference

A new method of fiber-optic based beam shaping is investigated both numerically and experimentally. A cylindrically symmetric method of lines (MoLs) is developed to simulate the device. The device is fabricated by fusion splicing a predetermined length of multimode fiber (MMF) to a single-mode fiber. The multimode interference (MMI) effects create ring-shaped field profiles at certain positions inside the MMF. The shaped beam can be used in medical applications requiring particular irradiation patterns.     

Kinetic,isotherm, and mechanism investigations of the removal of nitrate and nitrite from water by the synthesized hydrotalcite Mg–Al

Research on Chemical Intermediates - The objective of this work is to test the effectiveness of hydrotalcite as an adsorbent for the retention of nitrate and nitrite ions and to study the influence...     

Quantum mechanical ab initio calculations of the structural,electronic and optical properties of bulk gold nitrides

In the present work, the atomic and the electronic structures of Au₃N, AuN and AuN₂ are investigated using first-principles density-functional theory (DFT). We studied cohesive energy vs. volume data for a wide range of possible structures of these nitrides. Obtained data were fitted to a Birch-Murnaghan third-order equation of state (EOS) so as to identify the most likely candidates for the true crystal structure in this subset of the infinite parameter space, and to determine their equilibrium structural parameters. The analysis of the electronic properties was achieved by the calculations of the band structure and the total and partial density of states (DOS). Some possible pressure-induced structural phase transitions have been pointed out. Further, we carried out GW₀ calculations within the random-phase approximation (RPA) to the dielectric tensor to investigate the optical spectra of the experimentally suggested modification: Au₃N(D0₉). Obtained results are compared with experiment and with some available previous calculations.     

Voltammetric Label‐free Immunosensors for the Diagnosis of Cystic Echinococcosis

Cystic echinococcosis (CE) or hydatid disease is a parasitic infection caused by Echinococcus granulosus. Early serodiagnosis and continuous monitoring of the disease is very important for medical treatment. Here, we report the detecting of both echinococcus antigen and antibody for the diagnosis of hydatid disease using square wave voltammetry (SWV)‐based immunosensors. The gold electrodes were functionalized using cysteamine/phenylene diisothiocyanate linkers and used for the immunosensors fabrication. The hydatid antigen and antibody immunosensors were constructed by the immobilization of either purified rabbit polyclonal antibody or recombinant antigen B (AgB), respectively on the functionalized gold electrodes surfaces. The detection in both cases was achieved by following the change in the SWV reduction peak current of the ferro/ferricyanide redox couple upon antibody or antigen binding. These immunosensors enabled the detection of echinococcus antigen and antibody within a concentration range of 1 pg.mL^?1 to 1 μg.mL^?1 with detection limits of 0.4 pg.mL^?1 and 0.3 pg.mL^?1, respectively. A preliminary application of the developed immunosensor was performed in spiked serum sample showing good recovery percentages ranging from 102 to 110 % for both hydatid antibody and antigen detection. This easy‐to‐use, sensitive, and low cost quantitative method holds great promise for the early diagnosis of hydatid disease and thus, better managements and treatment outcomes.     

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.     

Antioxidant,Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC₅₀ of 1.30 ± 0.05 mg/mL in the DPPH test and an EC₅₀ equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC₅₀) was 7.8 ± 0.3 μL EO/L, while the effective concentration in the ingestion test (LC₅₀) was 15.0 ± 2.1 μL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.     

Antibacterial Mechanisms of Zinc Oxide Nanoparticle against Bacterial Food Pathogens Resistant to Beta-Lactam Antibiotics

The increase in β-lactam-resistant Gram-negative bacteria is a severe recurrent problem in the food industry for both producers and consumers. The development of nanotechnology and nanomaterial applications has transformed many features in food science. The antibacterial activity of zinc oxide nanoparticles (ZnO NPs) and their mechanism of action on β-lactam-resistant Gram-negative food pathogens, such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Serratia marcescens, Klebsiella pneumoniae, and Proteus mirabilis, are investigated in the present paper. The study results demonstrate that ZnO NPs possesses broad-spectrum action against these β-lactamase-producing strains. The minimal inhibitory and minimal bactericidal concentrations vary from 0.04 to 0.08 and 0.12 to 0.24 mg/mL, respectively. The ZnO NPs elevate the level of reactive oxygen species (ROS) and malondialdehyde in the bacterial cells as membrane lipid peroxidation. It has been confirmed from the transmission electron microscopy image of the treated bacterial cells that ZnO NPs diminish the permeable membrane, denature the intracellular proteins, cause DNA damage, and cause membrane leakage. Based on these findings, the action of ZnO NPs has been attributed to the fact that broad-spectrum antibacterial action against β-lactam-resistant Gram-negative food pathogens is mediated by Zn²⁺ ion-induced oxidative stress, actions via lipid peroxidation and membrane damage, subsequently resulting in depletion, leading to β-lactamase enzyme inhibition, intracellular protein inactivation, DNA damage, and eventually cell death. Based on the findings of the present study, ZnO NPs can be recommended as potent broad-spectrum antibacterial agents against β-lactam-resistant Gram-negative pathogenic strains.     

Antibacterial Activity of a Novel Oligosaccharide from Streptomyces californics against Erwinia carotovora subsp. Carotovora

The present study aims to characterize and predict models for antibacterial activity of a novel oligosaccharide from Streptomyces californics against Erwinia carotovora subsp. carotovora using an adaptive neuro-fuzzy inference system and an artificial neural network. The mathematical predication models were used to determine the optimal conditions to produce oligosaccharide and determine the relationship between the factors (pH, temperature, and time). The characteristics of the purified antibacterial agent were determined using ultraviolet spectroscopy (UV/Vis), infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (¹H- and ¹³C-NMR), and mass spectrometry (MS). The best performances for the model were 39.45 and 35.16 recorded at epoch 1 for E. carotovora Erw₅ and E. carotovora EMCC 1687, respectively. The coefficient (R²) of the training was more than 0.90. The highest antimicrobial production was recorded after 9 days at 25 °C and a pH of 6.2, at which more than 17 mm of the inhibition zone was obtained. The mass spectrum of antimicrobial agent (peak at R.T. = 3.433 of fraction 6) recorded two molecular ion peaks at m/z = 703.70 and m/z = 338.30, corresponding to molecular weights of 703.70 and 338.30 g/mol, respectively. The two molecular ion peaks matched well with the molecular formulas C₂₉H₅₃NO₁₈ and C₁₄H₂₆O₉, respectively, which were obtained from the elemental analysis result. A novel oligosaccharide from Streptomyces californics with potential activity against E. carotovora EMCC 1687 and E. carotovora Erw₅ was successfully isolated, purified, and characterized.