Selective and sensitive CQD-based sensing platform for Cu2+ detection in Wilson's disease.

Excessive Cu2+ intake can cause neurological disorders (e.g. Wilson's disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting.

Investigation on the Essential Oils of the Achillea Species: From Chemical Analysis to the In Silico Uptake against SARS-CoV-2 Main Protease.

In this study, phytochemicals extracted from three different Achillea genera were identified and analyzed to be screened for their interactions with the SARS-CoV-2 main protease. In particular, the antiviral potential of these natural products against the SARS-CoV-2 main protease was investigated, as was their effectiveness against the SARS-CoV-1 main protease as a standard (due to its high similarity with SARS-CoV-2). These enzymes play key roles in the proliferation of viral strains in the human cytological domain. GC-MS analysis was used to identify the essential oils of the Achillea species. Chemi-informatics tools, such as AutoDock 4.2.6, SwissADME, ProTox-II, and LigPlot, were used to investigate the action of the pharmacoactive compounds against the main proteases of SARS-CoV-1 and SARS-CoV-2. Based on the binding energies of kessanyl acetate, chavibetol (m-eugenol), farnesol, and 7-epi-ß-eudesmol were localized at the active site of the coronaviruses. Furthermore, these molecules, through hydrogen bonding with the amino acid residues of the active sites of viral proteins, were found to block the progression of SARS-CoV-2. Screening and computer analysis provided us with the opportunity to consider these molecules for further preclinical studies. Furthermore, considering their low toxicity, the data may pave the way for new in vitro and in vivo research on these natural inhibitors of the main SARS-CoV-2 protease.

Screening of honey bee pollen constituents against COVID-19: an emerging hot spot in targeting SARS-CoV-2-ACE-2 interaction.

The attachment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike to angiotensin-converting enzyme 2 (ACE-2) leads the cell fusion process, so spike blockade may be a promising therapy combating COVID-19. Bee pollen bioflavonoids with intrinsic bioactivities are of outmost importance to block SARS-CoV-2-ACE-2 interaction. Herein, we conducted a molecular docking assessment through natural phenolics/non-phenolics of pollen to investigate their affinity against SARS-CoV-2 spike. Finally, kaempferol 3-neohesperidoside 7-O-rhamnoside (compound a), quercetin 7-rhamnoside (compound b), delphinidin-3-O-(6-p-coumaroyl) glucoside (compound c), and luteolin-7-O-6″-malonylglucoside (compound d) showed the lowest binding affinity of -8.1, -7.7, -7.3 and -6.7 kcal/mol. The docking procedure was validated using protein-protein interactions between ACE-2 and SARS-CoV-2 RBD via HADDOCK webserver. MD simulations were fulfilled to investigate different ligands' effects on protein movements. Collectively, compound a may possess the potency to disturb the binding of SARS-CoV-2 spike-ACE-2, which can be on the call for further in vitro and in vivo study to investigate its antiviral potential against SARS-CoV-2.

A novel synthetised sulphonylhydrazone coumarin (E)-4-methyl-N'-(1-(3-oxo-3H-benzo[f]chromen-2- yl)ethylidene)benzenesulphonohydrazide protect against isoproterenol-induced myocardial infarction in rats by attenuating oxidative damage, biological changes and electrocardiogram.

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 µg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0 kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.

In silico evaluation of COVID-19 main protease interactions with honeybee natural products for discovery of high potential antiviral compounds.

This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. The six honeybee components, namely 3,4,5-Tricaffeoylquinic acid, Kaempferol-3-O-glucoside, (E)-2'-Geranyl-3',4',7-Trihydroxyflavanone, 6-Cinnamylchrysin, (+)-Pinoresinol, and (24E)-3-Oxo-27,28-dihydroxycycloart-24-en-26-oic acid, have represented the lowest binding energies of -9.0, -8.5, -8.2, -7.8, -7.7, -7.3 and -6.7 Kcal/mol, respectively. These natural inhibitors were then picked for further investigations on their pharmacokinetic features. Also a 150 ns of Molecular dynamics simulations were carried out in order to evaluate their effects on protein structure and dynamics. The 3, 4, 5-Tricaffeoylquinic acid is hopefully proposed for COVID-19 Mpro inhibition if further in vitro, in vivo, and clinical trial studies will approve its effectiveness against COVID-19.