Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2.

Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), and sterols (6%). Molecular docking was used to study the inhibitory activity of 69 identified compounds against SARS-CoV-2. In total, 12 out of 69 compounds were found to have active properties exhibiting SARS-CoV-2 inhibition. The binding scores of these molecules were significantly low, ranging from -7.8 to -5.6 kcal/mol. The interaction of oxatricyclo [20.8.0.0(7,16)] triaconta-1(22),7(16),9,13,23,29-hexaene with the active site is more efficient. Furthermore, the extract exhibited significant antimicrobial activity (in vitro) against Candida albicans, which was the most susceptible microorganism, followed by Bacillus cereus, Salmonella enterica, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. On the other hand, its antiviral activity was evaluated against HSV-1 and SARS-CoV-2, and the results showed a significant positive influence against HSV-1 (EC50 = 82.6 g/mL; CC50 = 162.9 g/mL; selectivity index = 1.9). In spite of this, no impact could be observed in terms of inhibiting the entry of SARS-CoV-2 in vitro.

Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2.

Siddha medicine is one of the oldest medical systems in the world and is believed to have originated more than 10,000 years ago and is prevalent across ancient Tamil land. It is undeniable that inhibitor preferences rise with increasing solubility in water due to the considerations pertaining to the bioavailability and the ease of which unabsorbed residues can be disposed of. In this study, we showed the phytochemical discrimination of Saussurea costus extracted with water at room temperature as a green extraction procedure. A total of 48 compounds were identified using gas chromatography-mass spectrometry (GC-MS). The fatty acids had a high phytochemical abundance at 73.8%, followed by tannins at 8.2%, carbohydrates at 6.9%, terpenoids at 4.3%, carboxylic acids at 2.5%, hydrocarbons at 2.4%, phenolic compounds at 0.2%, and sterols at 1.5%. Of these compounds, 22 were docked on the active side and on the catalytic dyad of His41 and Cys145 of the main protease of SARS-CoV-2 (Mpro). Eight active inhibitors were carbohydrates, five were fatty acids, three were terpenoids, two were carboxylic acids, one was a tannin, one was a phenolic compound, and one was a sterol. The best inhibitors were 4,8,13-Cyclotetradecatriene-1,3-diol, 1,5,9-trimethyl-12-(1-methylethyl), Andrographolide, and delta.4-Androstene-3.beta.,17.beta.-diol, with a binding affinity that ranged from -6.1 kcal/mol to -6.5 kcal/mol. The inhibitory effect of Saussurea costus of SARS-CoV-2 entry into the cell was studied using a pseudovirus with Spike proteins from the D614G variant and the VOC variants Gamma and Delta. Based on the viral cycle of SARS-CoV-2, our results suggest that the Saussurea costus aqueous extract has no virucidal effect and inhibits the virus in the events after cell entry. Furthermore, the biological activity of the aqueous extract was investigated against HSV-1 virus and two bacterial strains, namely Staphylococcus aureus ATCC BAA 1026 and Escherichia coli ATCC 9637. According to this study, an enormous number of water-soluble inhibitors were identified from Saussurea costus against the Mpro, and this is unprecedented as far as we know.

Intermolecular CH-π Electrons Interaction in Poly (9,9-dioctylfluorenyl-2,7-diyl) (PFO): An Experimental and Theoretical Study.

This study demonstrates the presence of CH-π interaction in poly [9,9-dioctylfluorenyl-2,7-diyl] (PFO-1) due to an aggregate formation of PFO-1 in the liquid state. The absorption spectra of PFO-1 in certain solvents at low concentrations showed a single band at 390 nm. However, when using high concentrations, a new band at 437 nm appeared. This band is due to the aggregate formation of PFO-1. The aggregate formation occurs as a result of the CH interaction of the n-alkyl side chains with π-electrons in the benzene ring. The optical characteristics of another conjugated polymer of poly [9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl] (PFO-2) were investigated to confirm the CH-π interaction. The absorption showed only one wavelength at 390 nm without any new band at the end of the spectrum, even at higher concentrations and lower temperatures. The main reason for the absence of aggregate formation in PFO-2 is the sterical hindrance caused by the branched alkyl side chains. In addition, Density Functional Theory (DFT) was used to compute the HOMO-LUMO transitions, electron charge distribution, and frontier molecular orbitals for each polymer. The Mulliken charge distribution and demonstrated a notable difference in the reactivity of the alkyl side chain, confirming the higher ability of PFO-1 to form CH-π bonds. docking model emphasized that the band at 437 nm could be attributed to the interaction between CH in the n-alkyl side chain and π bonds in the aromatic rings of PFO-1.

Caffeine and caffeine-containing pharmaceuticals as promising inhibitors for 3-chymotrypsin-like protease of SARS-CoV-2.

In December 2019, a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of a pulmonary disease called COVID-19, which killed thousands of people worldwide. Therefore, the necessity to find out the potential therapeutic pharmaceuticals is imperious. This study investigates the inhibitory effect of SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) using caffeine and caffeine-containing pharmaceuticals (3CPs) based on molecular dynamics simulations and free energy calculations by means of molecular mechanics-Poisson-Boltzmann surface area (MMPBSA) and molecular mechanics-generalized-Born surface area (MMGBSA). Of these 3CPs, seven drugs approved by the US-Food and Drug Administration have shown a good binding affinity to the catalytic residues of 3CLpro of His41 and Cys145: caffeine, theophylline, dyphylline, pentoxifylline, linagliptin, bromotheophylline and istradefylline. Their binding affinity score ranged from -4.9 to -8.6 kcal/mol. The molecular dynamic simulation in an aqueous solution of docked complexes demonstrated that the 3CPs conformations bound to the active sites of 3CLpro during 200 ns molecular dynamics simulations. The free energy of binding also confirms the stability of the 3CPs-3CLpro complexes. To our knowledge, this in silico study shows for the first time very inexpensive drugs available in large quantities that can be potential inhibitors against 3CLpro. In particular, the repurposing of linagliptin, and caffeine are recommended for COVID-19 treatment after in vitro, in vivo and clinical trial validation.Communicated by Ramaswamy H. Sarma.

Synthesis, anti-bacterial evaluation, DFT study and molecular docking as a potential 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2 inhibitors of a novel Schiff bases.

New Schiff bases {N'-(phenyl(pyridin-2-yl)methylene) isonicotinohydrazide (L1H), N1 -(naphthalen-1-yl)-N2 -(phenyl(pyridin-2-yl) methylidene) ethane-1,2-diamine (L2H), N-(6-chlorobenzo[d]thiazol-2-yl)-1-phenyl-1-(pyridin-2-yl) methanimine (L3H)}were synthesized by reaction of 2-benzoylpyridine with different amines (2-amino-6-chlorobenzothiazole, isonicotinohydrazide and N 1-(naphthalen-1-yl)ethane-1,2-diamine) and characterized by 1H-NMR, 13C-NMR, IR mass spectroscopy and elemental analysis. The compounds were assayed by the disc diffusion method for anti-bacterial against five pathogenic bacteria species (Staphylococcus aureus, Micrococcus luteus, Staphylococcus pyogenes, Bacillus subtilis, and E. coli). All prepared Schiff bases showed good activity compared to positive control (streptomycin), Moreover the L3H showed the highest activity against S. aureus, and M. luteus than the other compounds and streptomycin. In additional molecular docking studies with 3-chymotrypsin-like protease (3CLpro), the essential enzyme for SARS-CoV-2 proliferation. The rest of compounds have shown promising results as 3CLpro inhibitors interacting with the active sites of the enzymes. Finally, DFT 's estimated electrostatic molecular potential results were used to illustrate the molecular docking findings. The DFT calculations showed that L3H has the highest dipole moment and electrophilicity index. Interestingly, L2H of the largest energy gap ∆E = 2.49 eV, there are several hydrophilic interactions that could facilitate the binding with the receptors. All of these parameters could be shared to significantly affect the protein sites of binding affinity with different extent.

Inhibition of SARS-CoV-2 main protease 3CLpro by means of α-ketoamide and pyridone-containing pharmaceuticals using in silico molecular docking.

The coronavirus disease infections (COVID-19) caused by a new type of coronavirus (SARS-CoV-2) have been emerging in the entire world. Therefore, it is necessary to find out potential therapeutic pharmaceuticals for this disease. This study investigates the inhibitory effect of the 3-chymotrypsin-like protease of SARS-CoV-2 (3CLpro) using pharmaceuticals containing α-ketoamide group and pyridone ring based on molecular docking. Of these, eight pharmaceuticals approved by US-Food and Drug Administration have shown good contact with the catalytic residues of 3CLpro. They are telaprevir, temsirolimus, pimecrolimus, aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide. Their binding affinity score ranged from -5.6 to -7.4 kcal/mol. Hydrogen bonds were observed and reported. To the knowledge, this study report for the first time a compound that could be binding to ALA285, the new residue resulting from genetic modification of 3CLpro of SARS-CoV-2 that has increased its catalytic activity 3.6-fold compared with its predecessor 3CLpro of SARS-CoV. It is recommended that telaprevir, and pyridone-containing pharmaceuticals including aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide be repurposed for COVID-19 treatment after suitable validation and clinical trials.

Health risk from aflatoxins in processed meat products in Riyadh, KSA.

This study investigated the health risks associated with aflatoxins (AFs) in processed meat products (PMP) sold in Riyadh, Kingdom of Saudi Arabia. The occurrence and levels of AFs were assessed using high-performance liquid chromatography with fluorescence detection (HPLC-FD), whereas the cancer risk attributed to the consumption of meat products containing AFs was estimated by means of margin of exposure (MOE) on a scale of 100-600, representing high and low exposure, respectively. The results indicated that 37.5% of the samples were contaminated, with concentrations ranging from 0.30 to 52.93 µg/kg, at an average of 6.4 ± 12.58 µg/kg. The percentage contamination levels with total AFs higher than the permissible Saudi limit of 20 µg/kg were 4% of samples analysed and 10% of contaminated samples. AFB1 and AFG1 were the most prevalent toxins, followed by AFB2; AFG2 was not detected in any sample. The MOE was found to be 175 and 311 for total AFs in processed beef meat and poultry meat products, respectively. These results showed that the daily intake of AF-contaminated PMP may constitute a public health concern. To our knowledge, this is the first study to report the health risk associated with PMP contaminated with AFs.

Insight to aspirin sorption behavior on carbon nanotubes from aqueous solution: Thermodynamics, kinetics, influence of functionalization and solution parameters.

The chronic exposure to the pharmaceuticals and personal care products contaminants in water represent a serious public health problem to man and animal. We studied the removal of aspirin (Asp) as an example to these hazardous materials from an aqueous solution using functionalized (FMCNT) and pristine multiwall carbon nanotubes (PMCNT). The characterization of synthetic sorbents was examined with scanning electron energy-dispersive microscopy and transmission electron microscopy. The effects of adsorption time, sorbent mass, solution pH, ionic strength, and temperature were optimized. The functionalization increased the surface area from 151 to 181 m2 g-1. Consequently, the adsorption capacity increased from 41 mg g-1 to 58 mg g-1 for PMCNT and FMCNT, respectively. The results showed that the adsorption kinetic follows the pseudo-second-order model with very good agreement. Whereas, the adsorption mechanism study showed a partial agreement with the liquid-film diffusion model on PMCNT and FMCNT at 25 °C and 35 °C, respectively, with acceptable linear regression coefficients. The adsorption isotherm results revealed that the adsorption fits the Freundlich model. The thermodynamic study revealed that, Asp adsorption on both sorbents is exothermic, spontaneous and favorable. FMCNT showed relatively high removal efficiency when compared with the PMCNT when used for most of the conditions investigated.

An Ultrasound Assessed Extraction Combined with Ion-Pair HPLC Method and Risk Assessment of Nitrite and Nitrate in Cured Meat.

An accurate IPC-UV method was developed and validated for the determination of nitrite (NI) and nitrate (NA) in meat products. The best separation was achieved on a phenyl-hexyl column (150 mm × 4.6 mm, 3 µm) with a mobile phase composed of 25% acetonitrile and 75% buffer (2 mM disodium hydrogen phosphate and 3 mM tetrabutylammonium bromide, pH = 4). Eluents were monitored at 205 nm. Linearity ranges were 1.86 × 10-6-7.5 µg·ml-1 and 0.09-5.0 µg·ml-1 for NI and NA, respectively. The correlation coefficients were greater than 0.999 for NI and NA. This method was applied to a number of processed meat products in Riyadh (n = 155). NI ranged from 1.78 to 129.69 mg·kg-1, and NA ranged from 0.76 to 96.64 mg·kg-1. Results showed extensive use of NI and NA; however, concentrations were within the legal limit of Saudi Arabia except for one sample. Further, the risk assessment and dietary exposure have been estimated for both NI and NA.

Aflatoxin M1 in breast milk of nursing Sudanese mothers.

The presence of aflatoxin M1 (AFM1) in the breast milk of nursing Sudanese mothers was investigated using AOAC official method 980.21 as the extraction method and HPLC with fluorescence detector for separation and detection. Following informed consent, 94 breast milk samples of mothers were collected, and 51 samples were found to be positive for AFM1, with an average concentration of 0.401 ± 0.525 ng g(-1) and a maximum level of 2.561 ng g(-1). The volunteers completed a questionnaire concerning their dietary preferences. The data collected suggest that peanut butter, vegetable oils and rice are the main sources responsible for the AFM1 burden in breast milk. The toxin levels are alarmingly high, and indicate that Sudanese infants are exposed to high levels of AFM1. A wide range of harmful effects, and consequently health problems, can be expected due AFM1 toxicity.

Aflatoxins levels in vegetable oils in Khartoum State, Sudan.

Vegetable oil (n = 81) for human consumption from Khartoum State in Sudan were analyzed for aflatoxins (AFs), using high-performance liquid chromatography (HPLC) with fluorescence detection following extraction with methanol:water (80:20) and clean-up using petroleum ether. Sampling included sesame oil (n = 14), peanut oil (n = 21), and sunflower oil (n = 19) purchased from retail shops, and mixed oil produced by two local manufacturers (factory A, n = 15; factory B, n = 12). AF contamination was found in 80/81 (98.8%) samples, with total AF levels [Formula: see text] of 0.43-339.9 µg/kg and mean level of 57.5 µg/kg. All sesame oils had total AF levels that were much higher than the United States Food and Drug Administration acceptable limit of 20 µg/kg. The percentage of samples with total AF values <20 µg/kg in other oils varied and was 57.14% in peanut oil, 36.8% in sunflower oil, 66.7% (mixed oil from factory A), and 91.7% (mixed oil from factory B). In conclusion, the levels of total AFs in edible oil as available in Khartoum State are quite alarming. To reduce the health hazards for the consumers, an intervention strategy to manage AFs in food commodities from Sudan is urgently required.