Nature as a treasure trove of potential anti-SARS-CoV drug leads:a structural/mechanistic rationale

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M(pro)). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future

Authentication of saffron spice accessions from its common substitutes via a multiplex approach of UV/VIS fingerprints and UPLC/MS using molecular networking and chemometrics

Saffron is a spice revered for its unique flavor and health attributes often subjected to fraudulence. In this study, molecular networking as a visualization tool for UPLC/MS dataset of saffron and its common substitutes i.e. safflower and calendula (n = 21) was employed for determining genuineness of saffron and detecting its common substitutes i.e. safflower and calendula. Saffron was abundant in flavonol-O-glycosides and crocetin esters versus richness of flavanones/chalcones glycosides in safflower and cinnamates/terpenes in calendula. OPLS-DA identified differences in UPLC/MS profiles of different saffron accessions where oxo-hydroxy-undecenoic acid-O-hexoside was posed as saffron authentication marker and aided in discrimination between Spanish saffron of high quality from its inferior grade i.e. Iranian saffron along with crocetin di-O-gentiobiosyl ester and kaempferol-O-sophoroside. Kaempferol-O-neohesperidoside and N,N,N,-p-coumaroyl spermidine were characteristic safflower metabolites, whereas, calendulaglycoside C and di-O-caffeoyl quinic acid were unique to calendula. UV/VIS fingerprint spectral regions of picrocrocin (230-260 nm) and crocin derivatives (400-470 nm) were posed as being discriminatory of saffron authenticity and suggestive it can replace UPLC/MS in saffrom quality determination

A multiplex metabolomic approach for quality control of Spirulina supplement and its allied microalgae (Amphora & Chlorella) assisted by chemometrics and molecular networking

Abstract Microalgae species are of economic importance regarded as “green gold” being rich in bioactive compounds. Spirulina and Chlorella are the most popular microalgal species and are marketed as healthy food supplements. At the same time, Amphora holds potential as a source of healthy lipids and essential fatty acids. Yet, there are considerable variations in their reported chemical composition, and less is known about their compositional differences. A multiplexed metabolomic approach was adopted for the quality control (QC) of Spirulina supplements and to compare its constitutive metabolome to Chlorella and Amphora. The adopted protocol comprised gas chromatography-mass spectrometry (GC–MS), ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-HRMS/MS), and ultraviolet–visible spectrophotometry (UV/Vis) for mapping their primary and secondary metabolome. Interestingly, UPLC-HRMS/MS analysis delineated the abundance of fatty acids in Amphora versus glycolipids enrichment in Spirulina, and porphyrins were the main pigments identified in Spirulina, with scarce occurrence in Chlorella. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) analysis of GC–MS data set revealed palmitic acid, 3-mannobiose, and glyceryl-glycoside as being most enriched in Spirulina, versus sucrose and leucine in Chlorella and Amphora, respectively. Despite being of low discriminatory potential, UV/Vis OPLS-DA modeling showed that Spirulina was distinguished with the UV absorbances of carotenoids and chlorophyll pigments, as indicated by its OPLS-DA derived S-plot. Our study provides a QC approach for the analysis of the microalgal species and poses alternative spectral and compositional markers for their discrimination

LC–MS/MS based-comparative study of (S)-nicotine metabolism by microorganisms, mushroom and plant cultures: Parallels to its mammalian metabolic fate

The metabolic fate of nicotine using the cell cultures of microorganisms, mushroom and plants was explored using LC–MS/MS analysis. The study demonstrated parallels to phase I mammalian metabolism of nicotine and reported that nicotine was biotransformed into its N-oxide by Streptomyces fradiae culture. Moreover, it was metabolized in Pleurotus ostreatus culture into nornicotine, norcotinine and β-nicotyrine; whereas, cotinine and its 3′-hydroxylated derivative were the identified nicotine metabolic products in Pimpinella anisum cell culture. However, the microbial culture of Agaricus bisporus bioconverted nicotine into one of its derived-carcinogenic nitrosamines which is “4-(methylnitrosamino)-4-(3-pyridyl)butanal”. Mushroom and plant cell cultures were thus proven to be competent to microbial cultures in bioconverting nicotine into many of its previously reported metabolites. Convincingly, the obtained results highlighted the prospect of utilizing other species which are intrinsically-endowed with unique biocatalytic systems, such as mushrooms and plants, in the drug metabolic studies

Gas Chromatography/Mass Spectrometry-Based Metabolite Profiling of Nutrients and Antinutrients in Eight Lens and Lupinus Seeds (Fabaceae)

Lens culinaris and several Lupinus species are two legumes regarded as potential protein resources aside from their richness in phytochemicals. Consequently, characterization of their metabolite composition seems warranted to be considered as a sustainable commercial functional food. This study presents a discriminatory holistic approach for metabolite profiling in accessions of four lentil cultivars and four Lupinus species via gas chromatography/mass spectrometry. A total of 107 metabolites were identified, encompassing organic and amino acids, sugars, and sterols, along with antinutrients, <i>viz</i>., alkaloids and sugar phosphates. Among the examined specimens, four nutritionally valuable accessions ought to be prioritized for future breeding to include Lupinus hispanicus, enriched in organic (<i>ca.</i> 11.7%) and amino acids (<i>ca.</i> 5%), and Lupinus angustifolius, rich in sucrose (<i>ca.</i> 40%), along with two dark-colored lentil cultivars ‘verte du Puy’ and ‘Black Beluga’ enriched in peptides. Antinutrient chemicals were observed in Lupinus polyphyllus, owing to its high alkaloid content. Several species-specific markers were also revealed using multivariate data analyses

Facile synthesis of a luminescent carbon material from yogurt for the efficient photocatalytic degradation of methylene blue

The present study is focused on yogurt as a simple, inexpensive, abundant, and green source for the preparation of luminescent carbon material for enhancing the photodegradation of methylene blue (MB). It introduces an ecological and sustainable approach for the large-scale production of carbon material using the direct thermal annealing of yogurt in a muffle furnace. The size of the as-prepared carbon material is about 200-300 nm, with average particle size distribution of 355 nm. The material exhibits clear luminescence under illumination with ultraviolet light. The synthesized carbon material shows an outstanding degradation functionality of MB under the irradiation of ultraviolet (UV) light in aqueous media. Various dye degradation parameters such as initial dye concentration, catalyst dose, pH of dye solution, and scavenger effects have been investigated. The optimum MB concentration was found to be 2.3 x 10(-5) M with a degradation efficiency of 94.8%. The degradation was highly enhanced at pH 11 with a degradation efficiency of 98.11%. The degradation of MB under highly alkaline conditions was mainly governed by the high amount of hydroxyl radicals. Furthermore, the scavenger study confirmed that the hydroxyl radicals were mainly involved in the degradation process. The degradation kinetics of MB followed first order kinetics with large values of rate constant. The reusability was also studied to ensure the stability of the as-prepared carbon material during the degradation of MB. The preparation of carbon materials with efficient photosensitivity for the degradation of organic dyes from yogurt shows a green and innovative methodology. Therefore, it can be of great interest for future studies related to energy and environmental applications

Novel insights into the synergistic effects of selenium nanoparticles and metformin treatment of letrozole - induced polycystic ovarian syndrome: targeting PI3K/Akt signalling pathway, redox status and mitochondrial dysfunction in ovarian tissue

ABSTRACTPurpose Polycystic ovary syndrome (PCOS) has a series of reproductive and metabolic consequences. Although the link between PCOS, IR, and obesity, their impact on the pathogenesis of PCOS has yet to be determined. Dysfunction of PI3K/AKT pathway has been reported as the main cause of IR in PCOS. This study purposed to explore the effects of selenium nanoparticles (SeNPs) alone and combined with metformin (MET) in a PCOS-IR rat model.Methods After 3 weeks of treatment with SeNPs and/or MET, biochemical analysis of glycemic & lipid profiles, and serum reproductive hormones was performed. Inflammatory, oxidative stress, and mitochondrial dysfunction markers were determined colormetrically. The expression of PI3K and Akt genes were evaluated by Real-time PCR. Histopathological examination and Immunohistochemical analysis of Ki-67 expression were performed.Results The results showed that treatment with SeNPs and/or MET significantly attenuated insulin sensitivity, lipid profile, sex hormones levels, inflammatory, oxidative stress and mitochondrial functions markers. Additionally, PI3K and Akt genes expression were significantly upregulated with improved ovarian histopathological changes.Conclusion Combined SeNPs and MET therapy could be potential therapeutic agent for PCOS-IR model via modulation of the PI3K/Akt pathway, enhancing anti-inflammatory and anti-oxidant properties and altered mitochondrial functions.HighlightsThe strong relationship between obesity, insulin resistance, and polycystic ovarian syndrome.Disturbance of the PI3K/Akt signaling pathway is involved in the progression of polycystic ovary syndrome-insulin resistance (PCOS-IR).In PCOS-IR rats, combined SeNPs and metformin therapy considerably alleviated IR by acting on the PI3K/Akt signaling pathway.The combination of SeNPs and metformin clearly repaired ovarian polycystic pathogenesis and improved hormonal imbalance in PCOS-IR rats