Mechanistic QSAR modeling derived virtual screening, drug repurposing, ADMET and in-vitro evaluation to identify anticancer lead as lysine-specific demethylase 5a inhibitor.

A lysine-specific demethylase is an enzyme that selectively eliminates methyl groups from lysine residues. KDM5A, also known as JARID1A or RBP2, belongs to the KDM5 Jumonji histone demethylase subfamily. To identify novel molecules that interact with the LSD5A receptor, we created a quantitative structure-activity relationship (QSAR) model. A group of 435 compounds was used in a study of the quantitative relationship between structure and activity to guess the IC50 values for blocking LASD5A. We used a genetic algorithm-multilinear regression-based quantitative structure-activity connection model to forecast the bioactivity (PIC50) of 1615 food and drug administration pharmaceuticals from the zinc database with the goal of repurposing clinically used medications. We used molecular docking, molecular dynamic simulation modelling, and molecular mechanics generalised surface area analysis to investigate the molecule's binding mechanism. A genetic algorithm and multi-linear regression method were used to make six variable-based quantitative structure-activity relationship models that worked well (R2 = 0.8521, Q2LOO = 0.8438, and Q2LMO = 0.8414). ZINC000000538621 was found to be a new hit against LSD5A after a quantitative structure-activity relationship-based virtual screening of 1615 zinc food and drug administration compounds. The docking analysis revealed that the hit molecule 11 in the KDM5A binding pocket adopted a conformation similar to the pdb-6bh1 ligand (docking score: -8.61 kcal/mol). The results from molecular docking and the quantitative structure-activity relationship were complementary and consistent. The most active lead molecule 11, which has shown encouraging results, has good absorption, distribution, metabolism, and excretion (ADME) properties, and its toxicity has been shown to be minimal. In addition, the MTT assay of ZINC000000538621 with MCF-7 cell lines backs up the in silico studies. We used molecular mechanics generalise borne surface area analysis and a 200-ns molecular dynamics simulation to find structural motifs for KDM5A enzyme interactions. Thus, our strategy will likely expand food and drug administration molecule repurposing research to find better anticancer drugs and therapies.Communicated by Ramaswamy H. Sarma.

Pharmacological Basis for the Antidiarrheal and Antispasmodic Effects of Cuminaldehyde in Experimental Animals: In Silico, Ex Vivo and In Vivo Studies.

BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.

Identification and characterization of a novel begomovirus, Withania leaf curl virus associated with leaf curl disease of Withania somnifera.

Begomovirus is the largest genus of the family Geminiviridae with wide host range and responsible for a considerable amount of economic damage to many important crops globally. Withania somnifera (Indian ginseng) is an important medicinal plant with high demand in pharmaceutical industries worldwide. During the routine survey in 2019, typical characteristic viral symptoms such as severe leaf curling, downward rolling of the leaves, vein clearing, and poor growth of Withania plants with 17-20% disease incidence were observed in Lucknow, India. Typical symptoms, abundant presence of whiteflies, PCR and RCA based detection indicated the amplification of ~ 2.7 kb and suspected the causal pathogen to be a begomovirus, associated with a betasatellite (~ 1.3 kb). Transmission electron microscopy revealed the presence of twinned particles of ~ 18-20 nm in diameter. Full genome sequencing (2758 bp) of the virus and its analysis showed only 88% sequence identity with the begomovirus sequences present in the database. Hence, based on the nomenclature guidelines we concluded that the virus associated with the present disease of W. somnifera is a novel begomovirus and its name is proposed as Withania leaf curl virus.

QSAR, Molecular Docking, MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads.

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm−multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69−0.87, F = 403.46−292.11, etc., internal validation parameters; Q2LOO = 0.69−0.86, Q2LMO = 0.69−0.86, CCCcv = 0.82−0.93, etc., or external validation parameters Q2F1 = 0.64−0.82, Q2F2 = 0.63−0.82, Q2F3 = 0.65−0.81, R2ext = 0.65−0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.

High Throughput Screening for Bioactive Components of Berberis baluchistanica Ahrendt Root and Their Functional Potential Assessment.

Berberis baluchistanica Ahrendt is a medicinal plant potentially known for the treatment of different diseases. The bioactive, antioxidant, nutritional components, and antimicrobial properties of crude ethanolic root extract of Berberis baluchistanica were evaluated in this study. The extract was analyzed for total phenolic, flavonoid, DPPH (2, 2-diphenyl-1-picryl-hydrazyl) scavenging ability, FRAP (ferric reducing antioxidant power), nutritional, and antimicrobial potentials. The alkaloids, tannins, cardiac glycosides, anthraquinones, coumarin, saponins, phenolics, flavonoids, steroids, and terpenoids were confirmed. The extract possessed DPPH radical inhibition with the IC50 of 1.125 mg/mL and FRAP % reduction activity with IC50 (0.912 mg/mL). Total phenolic 19.897 ± 4.8141 mg GAE/g and flavonoid 12.9876 ± 0.8388 mg QE/g contents were confirmed in the root. The extracts exhibit good antibacterial activity against a broad spectrum of food borne pathogens Pseudomonas aeruginosa, Salmonella typhi, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The highest inhibitory activity was against Escherichia coli23.30 ± 1.16 mm and lowest against Klebsiella pneumoniae7 ± 0.01 mm. Furthermore, the presence of various phytochemical constituents (plant secondary metabolites) was also confirmed with gas chromatography and mass spectroscopy analysis. Results disclosed the occurrence of more than 70 compounds possessing various medicinal properties supporting the traditional uses of root of Berberis baluchistanica in various medical complications indigenously.

Subclinical mastitis in dairy cows in south-Asian countries: a review of risk factors and etiology to prioritize control measures.

Mastitis is a major production disease, causing significant economic losses for dairy farmers in South-Asian countries, as well as other parts of the world. Udder health control programs (UHCP) have been established in developed countries as an effective strategy for mastitis control but have not yet been introduced in South-Asian low-income countries like Bangladesh, India, Pakistan, and Sri Lanka. To launch UHCP successfully in dairy herds in South-Asia, it is important to know the current prevalence and risk factors for subclinical mastitis (SCM). Therefore, a narrative literature review was conducted with the aim to describe the dairy sector, the prevalence of SCM and its causal agents, risk factors for mastitis occurrence and the control measures suggested by different studies conducted in the selected countries. The literature revealed that India had the highest cattle population. Milking was mainly done by hand in all of the studied countries. Stall feeding was done in Bangladesh and Sri Lanka and limited access to grazing was also reported in some farms in India and Pakistan. There was substantial variation in the prevalence of SCM between studies in all 4 countries, ranging from about 20% to about 80%, but the average prevalence across all studies was high (50%). The most common causal agents for SCM were non-aureus staphylococci (NAS), Staphylococcus (S.) aureus, Streptococcus spp. and Escherichia (E.) coli. The management related risk factors reported for SCM were stall feeding of cows, a higher stock density, cracked floors, open drains, the presence of flies, poor drainage, peri-parturient diseases, infrequent dung removal and earth floors. The control measures suggested in these studies were to improve the hygiene and sanitation of cows, to improve the cleanliness of farms and milker's hands, to apply dry cow therapy, supplementing micronutrients and routine screening for SCM combined with taking intervention measures like isolation of cows or milking infected cows last, and proper treatment. Also, full hand milking, complete milking, machine milking, and providing feed and water immediately after milking have been recommended. Finally, we show that current literature often studies the same set of (non-manageable) risk factors, so more research is needed to obtain a comprehensive picture of the determinants of SCM. Randomized controlled trials are needed to truly quantify the effect of intervention under field conditions. Altogether, our work gives an overview of the udder health situation in South-Asia and provides the basis for the design of UHCP in this region.

A Deep Look into the Microbiology and Chemistry of Froth Treatment Tailings: A Review.

In Alberta's Athabasca oil sands region (AOSR), over 1.25 billion m3 of tailings waste from the bitumen extraction process are stored in tailings ponds. Fugitive emissions associated with residual hydrocarbons in tailings ponds pose an environmental concern and include greenhouse gases (GHGs), reduced sulphur compounds (RSCs), and volatile organic compounds (VOCs). Froth treatment tailings (FTT) are a specific type of tailings waste stream from the bitumen froth treatment process that contains bioavailable diluent: either naphtha or paraffins. Tailings ponds that receive FTT are associated with the highest levels of biogenic gas production, as diverse microbial communities biodegrade the residual diluent. In this review, current literature regarding the composition, chemical analysis, and microbial degradation of FTT and its constituents is presented in order to provide a more complete understanding of the complex chemistry and biological processes related to fugitive emissions from tailings ponds receiving FTT. Characterizing the composition and biodegradation of FTT is important from an environmental perspective to better predict emissions from tailings ponds and guide tailings pond management decisions.

16S rRNA gene-based microbiome analysis identifies candidate bacterial strains that increase the storage time of potato tubers.

In the past, the potato plant microbiota and rhizosphere have been studied in detail to improve plant growth and fitness. However, less is known about the postharvest potato tuber microbiome and its role in storage stability. The storage stability of potatoes depends on genotype and storage conditions, but the soil in which tubers were grown could also play a role. To understand the ecology and functional role of the postharvest potato microbiota, we planted four potato varieties in five soil types and monitored them until the tubers started sprouting. During storage, the bacterial community of tubers was analysed by next-generation sequencing of the 16S rRNA gene amplicons. The potato tubers exhibited soil-dependent differences in sprouting behaviour. The statistical analysis revealed a strong shift of the tuber-associated bacterial community from harvest to dormancy break. By combining indicator species analysis and a correlation matrix, we predicted associations between members of the bacterial community and tuber sprouting behaviour. Based on this, we identified Flavobacterium sp. isolates, which were able to influence sprouting behaviour by inhibiting potato bud outgrowth.

Exogenous Application of Salicylic Acid and Hydrogen Peroxide Ameliorate Cadmium Stress in Milk Thistle by Enhancing Morpho-Physiological Attributes Grown at Two Different Altitudes.

Cadmium (Cd+2) is a potential and widespread toxic environmental pollutant, mainly derived from a rapid industrial process that has inhibitory effects on growth, physiological, and biochemical attributes of various plant species, including medicinal plants such as Silybum marianum L. Gaertn commonly known as milk thistle. Plant signaling molecules, when applied exogenously, help to enhance/activate endogenous biosynthesis of potentially important signaling molecules and antioxidants that boost tolerance against various abiotic stresses, e.g., heavy metal stress. The present study documented the protective role of salicylic acid (SA;0.25 µM) and hydrogen peroxide (H2O2; 10 µM) priming, foliar spray, and combinational treatments in reducing Cd+2 toxicity (500 µM) in milk thistle grown at two diverse ecological zones of Balochistan Province of Pakistan i.e., Quetta (Qta) and Turbat (Tbt). The morpho-physiological and biochemical attributes of milk thistle were significantly affected by Cd+2 toxicity; however, priming and foliar spray of SA and H2O2 significantly improved the growth attributes (root/shoot length, leaf area, and root/shoot fresh and dry weight), photosynthetic pigments (Chl a, b, and carotenoids) and secondary metabolites (Anthocyanin, Soluble phenolics, and Tannins) at both altitudes by suppressing the negative impact of Cd+2. However, the oxidative damage parameters, i.e., MDA and H2O2, decreased astonishingly under the treatment of signaling molecules, thereby protecting membrane integrity under Cd+2 stress. The morphological variations were profound at the low altitude (Tbt) as compared to the high altitude (Qta). Interestingly, the physiological and biochemical attributes at both altitudes improved under SA and H2O2 treatments, thus hampered the toxic effect of Cd+2. These signaling compounds enhanced tolerance of plants under heavy metal stress conditions with the consideration of altitudinal, and ambient temperature variations remain to be the key concerns.

A systematic comparison of commercially produced struvite: Quantities, qualities and soil-maize phosphorus availability.

Production of struvite (MgNH4PO4·6H2O) from waste streams is increasingly implemented to recover phosphorus (P), which is listed as a critical raw material in the European Union (EU). To facilitate EU-wide trade of P-containing secondary raw materials such as struvite, the EU issued a revised fertilizer regulation in 2019. A comprehensive overview of the supply of struvite and its quality is presently missing. This study aimed: i) to determine the current EU struvite production volumes, ii) to evaluate all legislated physicochemical characteristics and pathogen content of European struvite against newly set regulatory limits, and iii) to compare not-regulated struvite characteristics. It is estimated that in 2020, between 990 and 1250 ton P are recovered as struvite in the EU. Struvite from 24 European production plants, accounting for 30% of the 80 struvite installations worldwide was sampled. Three samples failed the physicochemical legal limits; one had a P content of <7% and three exceeded the organic carbon content of 3% dry weight (DW). Mineralogical analysis revealed that six samples had a struvite content of 80-90% DW, and 13 samples a content of >90% DW. All samples showed a heavy metal content below the legal limits. Microbiological analyses indicated that struvite may exceed certain legal limits. Differences in morphology and particle size distribution were observed for struvite sourced from digestate (rod shaped; transparent; 82 mass% < 1 mm), dewatering liquor (spherical; opaque; 65 mass% 1-2 mm) and effluent from upflow anaerobic sludge blanket reactor processing potato wastewater (spherical; opaque; 51 mass% < 1 mm and 34 mass% > 2 mm). A uniform soil-plant P-availability pattern of 3.5-6.5 mg P/L soil/d over a 28 days sampling period was observed. No differences for plant biomass yield were observed. In conclusion, the results highlight the suitability of most struvite to enter the EU fertilizer market.

In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels.

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration-response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.

Data on degradome sequencing and analysis from mock-inoculated and Fusarium oxysporum treated leaves samples in Persicaria minor.

Degradome sequencing referred as parallel analysis of RNA ends (PARE) by modifying 5'-rapid amplification of cDNA ends (RACE) with deep sequencing method. Deep sequencing of 5' products allow the determination of cleavage sites through the mapping of degradome fragments against small RNAs (miRNA or siRNA) on a large scale. Here, we carried out degradome sequencing in medicinal plant, Persicaria minor, to identify cleavage sites in small RNA libraries in control (mock-inoculated) and Fusarium oxysporum treated plants. The degradome library consisted of both control and treated samples which were pooled together during library preparation and named as D4. The D4 dataset have been deposited at GenBank under accession number SRX3921398, https://www.ncbi.nlm.nih.gov/sra/SRX3921398.

The first horse herders and the impact of early Bronze Age steppe expansions into Asia.

The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (~3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.

Small RNA-seq analysis in response to methyl jasmonate and abscisic acid treatment in Persicaria minor.

Persicaria minor (Kesum) is an important medicinal plant with high level of secondary metabolite contents, especially, terpenoids and flavonoids. Previous studies have revealed that application of exogenous phytohormone could increase secondary metabolite contents of the plant. MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in various biological processes. In order to explore the possible role of miRNA in the regulation of these phytohormones signaling pathway and uncovering their potential correlation, we, for the first time, have generated the smallRNA library of Kesum plant. The library was developed in response to methyl jasmonate (MJ) and abscisic acid (ABA) treatment by using next-generation sequencing technology. Raw reads have been deposited to SRA database with the accession numbers, SRX2655642 and SRX2655643 (MJ-treated), SRXSRX2655644 and SRX2655645 (ABA-treated) and SRX2655646and SRX2655647 (Control).

Small RNA sequencing for secondary metabolite analysis in Persicaria minor.

Persicaria minor (kesum) is an important medicinal plant and commonly found in southeast countries; Malaysia, Thailand, Indonesia, and Vietnam. This plant is enriched with a variety of secondary metabolites (SMs), and among these SMs, terpenoids are in high abundance. Terpenoids are comprised of many valuable biomolecules which have well-established role in agriculture and pharmaceutical industry. In P. minor, for the first time, we have generated small RNAs data sets, which can be used as tool in deciphering their roles in terpenoid biosynthesis pathways. Fungal pathogen, Fusarium oxysporum was used as elicitor to trigger SMs biosynthesis in P. minor. Raw reads and small RNA analysis data have already been deposited at GenBank under the accessions; SRX2645684 (Fusarium-treated), SRX2645685 (Fusarium-treated), SRX2645686 (mock-infected), and SRX2645687 (mock-infected).

Enantioselective GC Analysis of C3-Oxygenatedp-Menthane type Indian Mentha spicata var. viridis 'Ganga' Essential Oil.

Essential oil of Mentha spicata L. var. viridis 'Ganga', an indigenously developed variety, was chemically profiled using various gas chromatographic techniques. Piperitenone oxide was characterized as the most exclusive constituent (69.7%) along with a new C3-oxygenated p-menthane alcohol,- diosphenolene (1.6%). Enantiomeric discrimination revealed (4S)-(-)-limonene, (R)-(-)-linalool and (lS,2S)-(+)-piperitenone oxide as predominant enantiomers. The oil contained mainly C3-oxygenated p-menthane monoterpenoids, which are distinctive of peppermint, instead of the characteristic C6-oxygenated class of spearmint. The present findings will aid in understanding the pathway and cause of C3-oxygenation in a spearmint taxon. The essential oil and pure piperitenone oxide showed growth inhibiting properties and thus, may be utilized in antifungal preparations for disease management of medicinal and aromatic plants.

Sweet sorghum bagasse and corn stover serving as substrates for producing sophorolipids.

To make the process of producing sophorolipids by Candida bombicola truly sustainable, we investigated production of these biosurfactants on biomass hydrolysates. This study revealed: (1) yield of sophorolipds on bagasse hydrolysate decreased from 0.56 to 0.54 and to 0.37 g/g carbon source when yellow grease was dosed at 10, 40 and 60 g/L, respectively. In the same order, concentration of sophorolipids was 35.9, 41.9, and 39.3 g/L; (2) under similar conditions, sophorolipid yield was 0.12, 0.05 and 0.04 g/g carbon source when corn stover hydrolysate was mixed with soybean oil at 10, 20 and 40 g/L. Sophorolipid concentration was 11.6, 4.9, and 3.9 g/L for the three oil doses from low to high; and (3) when corn stover hydrolysate and yellow grease served as the substrates for cultivating the yeast in a fermentor, sophorolipid concentration reached 52.1 g/L. Upon further optimization, sophorolipids production from ligocellulose will be indeed sustainable.

In silico and in vitro Studies on Begomovirus Induced Andrographolide Biosynthesis Pathway in Andrographis Paniculata for Combating Inflammation and Cancer.

Andrographolide and neoandrographolide are major bioactive molecules of Andrographis paniculata, a well-known medicinal plant. These molecules exhibited varying degrees of anti-inflammatory and anticancer activities in-vitro and in-vivo. Role of begomovirus protein C2/TrAP in biosynthesis of andrographolide was identified through molecular modeling, docking and predicted results were substantiated by in vitro studies. Homology molecular modeling and molecular docking were performed to study the binding conformations and different bonding behaviors, in order to reveal the possible mechanism of action behind higher accumulation of andrographolide. It was concluded that C2/TrAP inhibit the activation of SNF1-Related Protein Kinase-1 (SnRK1) in terpenoid pathway and removes the negative regulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) by SnRK1, leading to higher accumulation of andrographolide and neoandrographolide in begomovirus infected plants. The binding site residues of SnRK1 docked with C2/TrAP were found to be associated with ATP binding site, substrate binding site and activation loop. Predicted results were also validated by HPTLC. This study provides important insights into understanding the role of viral protein in altering the regulation of biosynthesis of andrographolide and could be used in future research to develop biomimetic methods for increasing the production of such phytometabolites having anti-cancerous and anti-inflammatory properties.

Eclipta yellow vein virus enhances chlorophyll destruction, singlet oxygen production and alters endogenous redox status in Andrographis paniculata.

The infection of Eclipta yellow vein virus [EcYVV-IN, Accession No. KC476655], recently reported for the first time, on Andrographis paniculata was studied for redox-mediated alteration mechanism in infected plants. A. paniculata, an important medicinal plant, is used in traditional Indian, Chinese and modern system of medicine. Andrographolide, one of the foremost components of this plant, is known for its varied pharmacological properties. Our investigation provides insight into the effect of virus-induced changes in the singlet oxygen quenching due to the alteration in pigment content (chlorophyll and carotenoids) as well as activation of plant secondary metabolism along with defense activation leading to changes in enzymatic and non-enzymatic redox status. Due to infection, a reduction in carotenoid content was observed which leads to reduced quenching of singlet oxygen. An increased level of enzymatic (SOD and APX) and non-enzymatic antioxidant (DPPH, FRAP, RP, NO, TAC and TP) activities were also observed in virus-infected plants with a positive correlation (>0.9). However, CAT activity was diminished which could be either due to its proteolytic degradation or inactivation by superoxide anions (O(2-.)), NO or peroxynitrite radicals. A significant (p < 0.05) increase in total phenolic content was observed in the infected plants while no considerable difference was seen in the total flavonoid content. Our results highlighted the alteration in redox status caused by virus-induced biotic stress on the plants and could be useful for understanding the after effects of viral infection This study could also be helpful in developing biomimetic methods for improving the production of secondary metabolites of pharmaceutical importance.

Sophorolipid production from biomass hydrolysates.

Although extensive research has been conducted on producing sophorolipids using Candida (Starmerella) bombicola from pure sugars and various oil sources, production of this biosurfactant has not been evaluated when cells are cultivated in lignocellulosic hydrolysates. Here, we report for the first time that C. bombicola is capable of producing sophorolipids on hydrolysates derived from sweet sorghum bagasse and corn fiber. Without oil supplementation, a sophorolipid concentration of 3.6 and 1.0 g/L was detected from cultures with bagasse and corn fiber hydrolysates, respectively. With the addition of soybean oil at 100 g/L, the yield of sophorolipids from these two hydrolysates in the same order was 84.6 and 15.6 g/L. Surprisingly, C. bombicola consumed all monomeric sugars and nonsugar compounds in the hydrolysates, and cultures with bagasse hydrolysates had higher yield of sophorolipids than those from a standard medium which contained pure glucose at the same concentration.