Glycosidic vs. Aglycol Form of Natural Products as Putative Tyrosinase Inhibitors

Numerous natural products and designed molecules have been evaluated as tyrosinase inhibitors that impede enzymes’ oxidation activity. In the present study, new potent natural inhibitors were retrieved from the ZINC database by the similarity-screening of 37 previously reported tyrosinase inhibitors. The screening resulted in 42 candidate inhibitory molecules that were categorized into five groups. Molecular-docking analysis for these compounds, as well as for three others known for their inhibition activity (caffeic acid, naringenin, and gallic acid), was carried out against the tyrosinase structure from Agaricus bisporus (AbTYR). The top-scoring compounds were used for further comparative analysis with their corresponding naturally occurring glycosides. The results suggested that the glycosylated inhibitors could interact better with the enzyme than their aglycon forms. In order to further examine the role of the sugar side group of potent tyrosinase inhibitors, the dynamic behavior of two such pairs of glycosidic/aglycol forms (naringin–naringenin and icariin–icaritin) in their complexes with the enzyme were studied by means of 20-ns MD simulations. The increased number of intermolecular hydrogen bonds and their augmented lifetime between AbTYR and the glycosidic analogues showed that the naringin and icariin molecules form more stable complexes than naringenin and icaritin with tyrosinase, and thus are more potent inhibitors.

An integrated method for optimized identification of effective natural inhibitors against SARS-CoV-2 3CLpro

The current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.

Determining the effect of natural inhibitors on sesame meal degradability using in vitro three step method

The aim of this experiment was to investigate the beneficial effect of monensin, tannic acid and cinnamon essential oil addition on sesame meal degradability by the three-step in vitro method. The effect of experimental additives on the degradability of sesame meal in the rumen, after rumen and in the whole gastrointestinal tract was significant (P<0.05). The in vitro ruminal and intestinal digestibility of sesame meal crude protein with experimental additives was in the range of 76 to 84% and 49 to 60%, respectively. The intestinal degradability of crude protein increased with the addition of cinnamon essential oil (about 10%). Addition of monensin, tannic acid, and cinnamon essential oil significantly increased the degradability of Neutral Detergent Fiber (NDF) and Acid Detergent Fiber (ADF) in the rumen, intestines and the whole gastrointestinal tract. The results showed that cinnamon essential oil (125 mg/L) increased the degradability of dry matter (DM), organic matter (OM), crude protein (CP), ADF and NDF in the rumen, after rumen and the whole digestive tract compared to all treatments (P<0.05). The results showed that addition of tannic acid (100 mg/L) decreased the disappearance of crude protein in the rumen, while it increased crude protein’s disappearance in the after rumen (P<0.05).

In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.

A Review on the Relationship between Matrix Metalloproteinases (Mmps) and their Natural Inhibitors (Tissue Inhibitors Of Matrix Metalloproteinases [Timps]) and the Success of an Autologous Arteriovenous Fistula (Avf)

Since its introduction by Brescia and Cimino in 1966, arteriovenous fistula has been regarded as the best vascular access for haemodialysis purpose. However, it’s not without any drawbacks which has cost over USD1 billion in the United States alone to rectify them. Intimal hyperplasia has been shown to be a major contributory factor to this development. Intimal hyperplasia is a complex molecular process resulting in unwarranted accumulation of contractile smooth muscle cells, myofibroblasts, fibroblasts, and macrophages. There is an increasing amount of evidence suggesting that matrix metalloproteinases (MMPs) and its natural inhibitors (tissue inhibitors of matrix metalloproteinases ([TIMPs]) play a pivotal role in the development of intimal hyperplasia. Our purpose of writing this review article is to examine these evidences and to suggest of what future research questions need to be answered to further strengthen and clarify this relationship.