Computational insights into the role of structurally diverse plant secondary metabolites as inhibitors against Imidazole Glycerol Phosphate Dehydratase of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is one of the major causes of death worldwide and there is a pressing need for the development of novel drug leads. The Imidazole Glycerol Phosphate Dehydratase (IGPD) of Mtb is one of the key enzymes in the histidine biosynthesis pathway and has been recognized as the potentially underexploited drug target for anti-tuberculosis treatment. In the present study, 6063 structurally diverse plant secondary metabolites (PSM) were screened for their efficiency in inhibiting the catalytic activity of IGPD through molecular docking. The top 150 PSMs with the lowest binding energy represent the chemical classes, including Tannins (34%), Flavonoid Glycosides (14%), Terpene Glycosides (10%), Steroid Lactones (9.3%), Flavonoids (6.6%), Steroidal Glycosides (4.6%), etc. Bismahanine, Ashwagandhanolide, and Daurisoline form stable IGPD-inhibitor complexes with binding free energies of -291.3 ± 16.5, -279.0 ± 25.0, and -279.8 ± 17.6 KJ/mol, respectively, as determined by molecular dynamics simulations. These PSM demonstrated strong H-bond interactions with the amino acid residues Ile279, Arg281, and Lys276 in the catalytic region of IGPD, as revealed by structural snapshots. On the basis of our findings, these three PSM could be considered as possible leads against IGPD and should be explored in vitro and in vivo.Communicated by Ramaswamy H. Sarma.

Imidazole Glycerol Phosphate Dehydratase (IGPD) is an unexplored drug target in tuberculosis therapy.Inhibitory potential of 6063 plant secondary metabolites (PSM) against IGPD enzyme was studied.Ensemble docking and structural-activity relationship studies ascertained the group of diverse molecules.MD simulations predicted Bismahanine and Ashwagandhanolide as possible inhibitors of IGPD.

Studies on temperature impact (sudden and gradual) of the white-leg shrimp Litopenaeus vannamei.

In the present study, the effect of temperature shock (sudden and gradual) by increasing water temperature from 28 °C to 40 °C on survival, behavioral responses and immunological changes in Litopenaeus vannamei (L. vannamei) was studied. In sudden temperature shock, experimental groups were maintained at different temperature ranges such as 28 °C- 31 °C; 28 °C-34 °C; 28 °C-37 °C and 28 °C-40 °C along with 28 °C as control. For gradual temperature shock experiments, the initial water temperature was maintained at 28 °C for 24 h in control and then increased to 1 °C for every 24 h until reaching 40 °C. On reaching the final temperature of 40 °C, it was kept stable for 120 h. Results indicated that the increasing water temperature (sudden shock) affected survival, behavioral responses and immunological parameter. No shrimp survived at 40 °C treatment (sudden), whereas in the gradual temperature shock experiment 20% of animals survived at 40 °C. The increasing water temperature had no effects on behavioral responses up to 37 °C (gradual), but at 40 °C the observation of muscle cramps, low swimming rate, no feeding, muscle and hepatopancreas color turned whitish. Overall, the results suggest that L. vannamei can tolerate water temperature up to 34 °C under sudden shock and 37 °C under gradual shock conditions. This study reveals that shrimp L. vannamei can self-regulate to a certain extent of temperature variation in the environment.

A comparative study on chitosan nanoparticle synthesis methodologies for application in aquaculture through toxicity studies.

Chitosan nanoparticles (CSNPs) have been recently used for various applications in aquaculture, especially as drug carriers. The aim of this study was to synthesise and investigate a superlative method of CSNP synthesis for application in aquaculture through aquaculture-based toxicology screening methods. Two different methods were analysed: the first a direct ionic gelation method (A) and the other involving a low-molecular-weight chitosan microparticle intermediate method (B). Dynamic light scattering characterisation revealed that the CSNP particle sizes were 192.7 ± 11.8 and 22.9 nm from methods A and B, respectively. The LC50 values for brine shrimp toxicity were found to be 1.51 and 0.02 ppt in 24 h for methods A and B, respectively. Acute toxicity studies in Litopenaeus vannamei rendered LC50 values of 3235.94 and 2884.03 ppt in 24 h for methods A and B, respectively. Zebrafish toxicity studies revealed mortality rates of 21.67% and 55% at 20 mg/L concentration for methods A and B, respectively, with an increased expression of intracellular reactive oxygen species in method B. From these findings, it can be concluded that a comparatively reduced toxicity of CSNPs derived from ionic gelation method makes it more appropriate for application in aquaculture.

In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis.

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

Multi-elemental concentration in different body parts of Sepiella inermis by inductively coupled plasma mass spectrometry.

The present study examined the accumulation of metal on Sepiella inermis from the Mudasalodai Landing Center, from southeast coastal region of India. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine metals including aluminium, boron, cadmium, cobalt, chromium, copper, iron, manganese, magnesium, nickel, lead and zinc. The results showed that metal concentration in S. inermis detected in the head, arm, mantle, eye, ink, liver and nidamental gland with higher concentration of magnesium up to 992.78 mg/kg, and tentacle showed maximum concentration of aluminium 306.72 mg/kg. Further, copper found in low concentration ranges from 0.04 to 0.55 mg/kg in different parts of S. inermis. Heavy metal like cadmium detected high in tentacle with 0.24 mg/kg, and the manganese present in eye was 0.55 mg/kg. However, no accumulation of nickel was found in the tentacle part.

Chemical structure and biological properties of a polysaccharide isolated from Pleurotus sajor-caju.

Herein, a polysaccharide obtained from Pleurotus sajor-caju was fractionated via anion-exchange column chromatography and purified using gel permeation column chromatography. The chemical characterization of the polysaccharide indicated that it contained 90.16% total carbohydrate, 0% protein, 12.7% ash and 5.2% moisture; on the other hand, the carbon, hydrogen and nitrogen contents were found to be 31.53, 4.28 and 3.01%, respectively. The polysaccharide has the molecular weight of 79 kDa; the chemical structure of the polysaccharide is →6)α-d-Glciv(1→6)α-d-Glciii(1→6)ß-d-Glcii(1→6)α-d-Glci(1→units. The polysaccharide exhibited the DPPH radical scavenging activity of 21.67-68.35% at 10-160 µg ml-1, ABTS radical scavenging activity of 16.01-70.09% at 25-125 µg ml-1, superoxide radical scavenging activity of 24.31-73.64% at 50-250 µg ml-1, hydroxyl radical scavenging activity of 16.64-63.51% at 25-125 µg ml-1 and reducing power of 0.366-1.678% at 10-120 µg ml; further evaluation of the polysaccharide revealed its anticancer activity of 18.61-63.21% at 100-500 µg ml-1 concentration against the AGS human gastric carcinoma cell line. The active principle of the polysaccharide may be used in the food and pharmacological industry in the future.

Sulfated polysaccharide from Sargassum tenerrimum attenuates oxidative stress induced reactive oxygen species production in in vitro and in zebrafish model.

The sulfated polysaccharide (SP) was isolated from the brown alga S. tenerrimum. The chemical composition of SP composed of 57 ± 0.29% of total sugar, 1.14 ± 0.28% of protein and 25.6 ± 0.45% of sulfate. Elemental analysis of SP shows 28.8% of carbon, 4.02% of hydrogen and 0.29% of nitrogen. The molecular weight of SP was estimated as 31 kDa. Further, the SP was characterized through FT-IR, 1H-NMR, GC-MS, XRD and TGA analysis. The DPPH and ABTS radical scavenging activity of SP showed 34.03-62.70% and 22.94-38.04% at the concentration of 25-125 µg/mL respectively. In addition, SP exerted a protective role against H2O2 mediated oxidative stress in fibroblast cells through scavenging intracellular ROS. Furthermore, ROS generation and cell death were significantly decreased in SP treated zebrafish embryos at 150 µg/mL, whereas the survival rate was increased. The protective effect of SP against oxidative stress might be utilized in pharmacological industries.

Mineral and Trace Metal Concentrations in Seaweeds by Microwave-Assisted Digestion Method Followed by Quadrupole Inductively Coupled Plasma Mass Spectrometry.

This study reports the total concentrations of mineral and trace metals sodium, potassium, calcium, magnesium, phosphorus, iron, copper, zinc, and manganese in the seaweeds Padina tetrastromatica, Turbinaria ornate, Sargassum wightii, Sargassum swartzii, Gracilaria edulis, Ulva lactuca, Chaetomorpha antennina, and Halimeda opuntia collected from mandapam coastal regions, Southeast coast of India. Microwave-assisted digestion was used for sample preparation prior to mineral and trace metal analysis. Mineral and trace metal analyses were determined by inductively coupled plasma mass spectrometry. The ranges of concentrations of mineral and trace metals in algae were 27.04 ± 2.54-194.08 ± 2.36 mg/kg for manganese, 1.88 ± 0.10-121.5 ± 0.70 mg/kg for sodium, 6.5 ± 0.56-90.5 ± 2.12 mg/kg for magnesium, 59.07 ± 0.34-672 ± 2.82 mg/kg for potassium, 13.15 ± 2.08-135.13 ± 1.59 for sulfur, 0.003 ± 0.001-3.44 ± 0.13 mg/kg for cobalt, 0.39 ± 0.19-8.95 ± 0.38 mg/kg for copper, 0.72 ± 0.28-25.72 ± 0.39 mg/kg for zinc, and 6.01 ± 0.27-188.47 ± 1.92 mg/kg for iron.The results were evaluated statistically, and the significant difference was observed in the mean concentrations of all mineral and trace elements, except Co, Cu, and Zn, among the type of seaweeds.