Wild mushrooms from Ilgaz Mountain National Park (Western Black Sea, Turkey): element concentrations and their health risk assessment.

The purpose of this study was to determine Fe, Cd, Cr, Se, P, Cu, Mn, Zn, Al, Ca, Mg, and K contents of some edible (Chlorophyllum rhacodes, Clavariadelphus truncatus, Clitocybe nebularis, Hydnum repandum, Hygrophorus pudorinus, Infundibulicybe gibba, Lactarius deliciosus, L. piperatus, L. salmonicolor, Macrolepiota mastoidea, Russula grata, Suillus granulatus, and Tricholoma imbricatum), inedible (Amanita pantherina, Geastrum triplex, Gloeophyllum sepiarium, Hypholoma fasciculare, Phellinus vorax, Pholiota limonella, Russula anthracina, and Tapinella atrotomentosa), and poisonous mushroom species (Amanita pantherina and Hypholoma fasciculare) collected from Ilgaz Mountain National Park (Western Black Sea, Turkey). The element contents of the mushrooms were determined to be 18.0-1239.1, 0.2-4.6, 0.1-3.4, 0.2-3.2, 1.0-8.9, 3.3-59.9, 3.7-220.4, 21.3-154.1, 6.4-754.3, 15.8-17,473.0, 413.0-5943.0, and 2803.0-24,490.0 mg·kg-1, respectively. In addition to metal contents, the daily intakes of metal (DIM) and Health Risk Index (HRI) values of edible mushrooms were also calculated. Both DIM and HRI values of mushroom species except L. salmanicolor, M. mastoidea, and R. grata were within the legal limits. However, it was determined that the Fe content of L. salmanicolor and M. mastoidea and Cd content of R. grata were above the legal limits.

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties.

Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-)-epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-)-epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-)-epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.

Understanding the molecular interaction of SARS-CoV-2 spike mutants with ACE2 (angiotensin converting enzyme 2).

Covid-19 is a viral disease caused by the virus SARS-CoV-2 that spread worldwide and caused more than 4.3 million deaths. Moreover, SARS-CoV-2 still continues to evolve, and specifically the E484K, N501Y, and South Africa triple (K417N + E484K + N501Y) spike protein mutants remain as the 'escape' phenotypes. The aim of this study was to compare the interaction between the receptor binding domain (RBD) of the E484K, N501Y and South Africa triple spike variants and ACE2 with the interaction between wild-type spike RBD-ACE2 and to show whether the obtained binding affinities and conformations corraborate clinical findings. The structures of the RBDs of the E484K, N501Y and South Africa triple variants were generated with DS Studio v16 and energetically minimized using the CHARMM22 force field. Protein-protein dockings were performed in the HADDOCK server and the obtained wild-type and mutant spike-ACE2 complexes were submitted to 200-ns molecular dynamics simulations with subsequent free energy calculations using GROMACS. Based on docking binding affinities and free energy calculations the E484K, N501Y and triple mutant variants were found to interact stronger with the ACE2 than the wild-type spike. Interestingly, molecular dynamics and MM-PBSA results showed that E484K and spike triple mutant complexes were more stable than the N501Y one. Moreover, the E484K and South Africa triple mutants triggered greater conformational changes in the spike glycoprotein than N501Y. The E484K variant alone, or the combination of K417N + E484K + N501Y mutations induce significant conformational transitions in the spike glycoprotein, while increasing the spike-ACE2 binding affinity.Communicated by Ramaswamy H. Sarma.

Determination of the interaction between the receptor binding domain of 2019-nCoV spike protein, TMPRSS2, cathepsin B and cathepsin L, and glycosidic and aglycon forms of some flavonols.

The novel coronavirus (COVID-19, SARS-CoV-2) is a rapidly spreading disease with a high mortality. In this research, the interactions between specific flavonols and the 2019-nCoV receptor binding domain (RBD), transmembrane protease, serine 2 (TMPRSS2), and cathepsins (CatB and CatL) were analyzed. According to the relative binding capacity index (RBCI) calculated based on the free energy of binding and calculated inhibition constants, it was determined that robinin (ROB) and gossypetin (GOS) were the most effective flavonols on all targets. While the binding free energy of ROB with the spike glycoprotein RBD, TMPRSS2, CatB, and CatL were -5.02, -7.57, -10.10, and -6.11 kcal/mol, the values for GOS were -4.67, -5.24, -8.31, and -6.76, respectively. Furthermore, both compounds maintained their stability for at least 170 ns on respective targets in molecular dynamics simulations. The molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations also corroborated these data. Considering Lipinski's rule of five, ROB and GOS exhibited 3 (MW>500, N or O>10, NH or OH>5), and 1 (NH or OH>5) violations, respectively. Neither ROB nor GOS showed AMES toxicity or hepatotoxicity. The LD50 of these compounds in rats were 2.482 and 2.527 mol/kg, respectively. Therefore, we conclude that these compounds could be considered as alternative therapeutic agents in the treatment of COVID-19. However, the possible inhibitory effects of these compounds on cytochromes (CYPs) should be verified by in vitro or in vivo tests and their adverse effects on cellular energy metabolism should be minimized by performing molecular modifications if necessary.

Interaction of certain monoterpenoid hydrocarbons with the receptor binding domain of 2019 novel coronavirus (2019-nCoV), transmembrane serine protease 2 (TMPRSS2), cathepsin B, and cathepsin L (CatB/L) and their pharmacokinetic properties.

As of June 2020, the coronavirus disease 19 (COVID-19) caused by the 2019 new type coronavirus (2019-nCoV) infected more than 7,000,000 people worldwide and caused the death of more than 400,000 people. The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B (CatB), and cathepsin L (CatL)]. As a result of the relative binding capacity index (RBCI) analysis, carvone was found to be the most effective molecule against all targets when binding energy and predicted (theoretical) IC50 data were evaluated together. It was found to exhibit drug-likeness property according to the Lipinski's rule-of-five. Carvone has also been determined to be able to cross the blood-brain barrier (BBB) effectively, not a substrate for P-glycoprotein (P-gp), not to inhibit any of the cytochrome P molecules, and to have no toxic effects even on liver cells. In addition, the LD50 dose of carvone in rats was 1.707 mol/kg. Due to its interaction profile with target proteins and excellent pharmacokinetic properties, it has been concluded that carvone can be considered as an alternative agent in drug development studies against 2019-nCoV.

Medicinal Uses, Phytochemistry, and Pharmacology of Origanum onites (L.): A Review.

Origanum onites L., known as Turkish oregano, has great traditional, medicinal, preservative, and commercial importance. It is used for the treatment of several kinds of ailments, such as gastrointestinal disorders, diabetes, high cholesterol, leukemia, bronchitis, etc. In this review, traditional use, phytochemistry, and pharmacology of O. onites reported between 1988 and 2014 were discussed. This review was prepared based on literature survey on scientific journals and books from libraries and electronic sources, such as Web of Science, PubMed, Scopus, Google Scholar, etc. All databases were searched up to June 2014. Several different classes of terpenoids, triterpene acids, phenolic acids, hydroquinones, flavonoids, hydrocarbons, sterols, pigments, fatty acids, tocopherols, and inorganic compounds were detected mainly in the aerial parts of this plant. Pharmacological studies revealed that extracts obtained from several solvents and individual compounds exhibited antimicrobial, antiviral, antioxidant, insecticidal, anticancer, hepatoprotective, genotoxic, antidiabetic, cholinesterase inhibitory, anti-inflammatory, analgesic activities, etc. O. onites, in general, exhibited remarkable activity potential in almost all test systems. The results of toxicity studies indicated that O. onites did not show any significant toxicity and mutagenicity on Drosophila and Salmonella. Toxicity of the extracts/essential oils and also individual compounds should be evaluated on mammalian cells to ensure their safety. The bioactivity of individual compounds aside from terpenoids should also be assessed in detail. Additionally, mode of action for the bioactive compounds should be evaluated to understand the complex pharmacological effects of these phytochemicals.

Determination of in vitro antioxidative and antimicrobial properties and total phenolic contents of Ziziphora clinopodioides, Cyclotrichium niveum, and Mentha longifolia ssp. typhoides var. typhoides.

The aerial parts of Ziziphora clinopodioides, Cyclotrichium niveum, and Mentha longifolia ssp. typhoides var. typhoides were screened for their possible antioxidant and antimicrobial activities in addition to their penolic contents. Antioxidant activity was employed by two complementary test systems: 2,2'-diphenyl-1-picrylhydrazyl free radical scavenging and beta-carotene/linoleic acid. In the first case, Z. clinopodioides was superior to the other species with a 50% inhibitory concentration value of 37.73 +/- 1.18 microg/mg. Similar results were obtained from the beta-carotene/linoleic acid system. Inhibition capacity of the linoleic acid of Z. clinopodioides was 83.56 +/- 1.19%. Additionally, antioxidant activities of butylated hydroxytoluene, curcumin, and ascorbic acid were determined in parallel experiments. Methanol extracts obtained from the plants studied were found to have moderate antimicrobial activity against all microorganisms tested. In general, Z. clinopodioides extract exhibited stronger activity than the other extracts. On the other hand, Acinetobacter lwoffii and Candida krusei were the most sensitive microorganisms for the all extracts. The amount of the total phenolics was highest in Z. clinopodioides extract (129.55 +/- 2.26 microg/mg), followed by M. longifolia ssp. typhoides var. typhoides (93.47 +/-1.84 microg/mg). It is extremely important to note that there is a positive correlation between antioxidant activity potential and amount of phenolic compounds.