Identification of Concomitant Inhibitors against Glutamine Synthetase and Isocitrate Lyase in Mycobacterium tuberculosis from Natural Sources.

Tuberculosis (T.B.) is a disease that occurs due to infection by the bacterium, Mycobacterium tuberculosis (Mtb), which is responsible for millions of deaths every year. Due to the emergence of multidrug and extensive drug-resistant Mtb strains, there is an urgent need to develop more powerful drugs for inclusion in the current tuberculosis treatment regime. In this study, 1778 molecules from four medicinal plants, Azadirachta indica, Camellia sinensis, Adhatoda vasica, and Ginkgo biloba, were selected and docked against two chosen drug targets, namely, Glutamine Synthetase (G.S.) and Isocitrate Lyase (I.C.L.). Molecular Docking was performed using the Glide module of the SchrÓ§dinger suite to identify the best-performing ligands; the complexes formed by the best-performing ligands were further investigated for their binding stability via Molecular Dynamics Simulation of 100 ns. The present study suggests that Azadiradione from Azadirachta indica possesses the potential to inhibit Glutamine Synthetase and Isocitrate Lyase of M. tuberculosis concomitantly. The excellent docking score of the ligand and the stability of receptor-ligand complexes, coupled with the complete pharmacokinetic profile of Azadiradione, support the proposal of the small molecule, Azadiradione as a novel antitubercular agent. Further, wet lab analysis of Azadiradione may lead to the possible discovery of a novel antitubercular drug.

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19.

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNß and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of -5.752 and Glide gscore of -5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

Exploring the Bioactive Potentials of C60-AgNPs Nano-Composites against Malignancies and Microbial Infections.

At present, the potential role of the AgNPs/endo-fullerene molecule metal nano-composite has been evaluated over the biosystems in-vitro. The intra-atomic configuration of the fullerene molecule (C60) has been studied in-vitro for the anti-proliferative activity of human breast adenocarcinoma (MDA-MB-231) cell lines and antimicrobial activity against a few human pathogens that have been augmented with the pristine surface plasmonic electrons and antibiotic activity of AgNPs. Furthermore, FTIR revealed the basic vibrational signatures at ~3300 cm-1, 1023 cm-1, 1400 cm-1 for O-H, C-O, and C-H groups, respectively, for the carbon and oxygen atoms of the C60 molecule. NMR studies exhibited the different footprints and magnetic moments at ~7.285 ppm, explaining the unique underlying electrochemical attributes of the fullerene molecule. Such unique electronic and physico-chemical properties of the caged carbon structure raise hope for applications into the drug delivery domain. The in-vitro dose-dependent application of C60 elicits a toxic response against both the breast adenocarcinoma cell lines and pathogenic microbes. That enables the use of AgNPs decorated C60 endo fullerene molecules to design an effective anti-cancerous drug delivery and antimicrobial agent in the future, bringing a revolutionary change in the perspective of a treatment regime.

Reduced Graphene Oxide Nanosheets for Selective Picomolar Detection of Bovine Serum Albumin.

In this paper, ultra-low level selective detection of bovine serum albumin (BSA) has been demonstrated, based on chemically derived graphene i.e., reduced graphene oxide (RGO) nanosheets. The working principle of the sensor is based upon change in conductance of the RGO nanosheets with different concentration of BSA. The change in conductance is based on the charge transfer between BSA and functional groups of RGO. The morphological and structural characterizations of RGO nanosheets were carried out by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Raman spectroscopy is performed to further validate the interaction between RGO sensing layer and BSA molecules. Electrical impedance spectroscopy is performed to observe the impedance variation when BSA interacts with RGO. The sensor device exhibits sensitivity of 10 nA/pM. The lower limit of detection (LOD) of the sensor is found to be 1 pM and response time around 35 s, confirming very high sensitivity for BSA. All electrical (current-voltage) measurements were carried out at 2 V bias for low power operation. The sensor exhibits highest sensitivity at 30 °C and for RGO thickness ~4 nm. The RGO based sensor device is selective towards BSA when compared to proteins like L-Histidine, HSA, BHB and Biotin. Our results suggest that RGO based devices are promising for low-cost, portable and real time detection of BSA at room temperature.

Wet chemical development of CuO/GO nanocomposites: its augmented antimicrobial, antioxidant, and anticancerous activity.

This study employed a bottom-up technique to synthesize copper oxide (CuO) nanoparticles over hydrophilic graphene oxide (GO) nanosheets. The CuO/GO nanocomposite has been prepared using two selected precursors of copper nitrate and citric acid with an intermittent mixing of GO solutions. The synthesized Nanocomposites were characterized using different biophysical techniques like FT-IR, NMR, FE-SEM, and HR-TEM analyses. FT-IR analyses confirm the nanocomposites' successful formation, which is evident from the functional groups of C=C, C-O, and Cu-C stretching vibrations. Morphological analyses reveal the depositions of CuO nanoparticles over the planar rough GO sheets, which has been elucidated from the FE-SEM and HR-TEM analyses supported by respective EDAX analyses. The antimicrobial activities have been evident from the surface roughness and damages seen from the FE-SEM analyses. The CuO/GO sheets were tested against Gram-positive (e.g., Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa). It is evident that the intrinsic antibacterial activity of CuO/GO sheets, when combined in equal proportions, elicited a robust antibacterial activity when tested over Gram -ve representative bacteria Escherichia coli. The antioxidant behaviour of synthesized CuO/GO nanocomposite was evaluated by scavenging the free radicals of DPPH and ABTS. Moreover, the cytotoxic activity was also studied against epidermoid carcinoma cell line A-431. A brief mathematical formulation has been proposed in this study to uncover the possibilities of using the nanocomposites as potential drug candidates in theranostic applications in disease treatment and diagnosis. This study would help uncover the electronic properties that play in the nano-scaled system at the material-bio interface, which would aid in designing a sensitive nano-electromechanical device bearing both the therapeutic and diagnostic attributes heralding a new horizon in the health care systems.

Corrigendum: Anti-biofilm and Antibacterial Activities of Silver Nanoparticles Synthesized by the Reducing Activity of Phytoconstituents Present in the Indian Medicinal Plants.

[This corrects the article DOI: 10.3389/fmicb.2020.01143.].

Anti-biofilm and Antibacterial Activities of Silver Nanoparticles Synthesized by the Reducing Activity of Phytoconstituents Present in the Indian Medicinal Plants.

Biofilm forming from a variety of microbial pathogens can pose a serious health hazard that is difficult to combat. Nanotechnology, however, represents a new approach to fighting and eradicating biofilm-forming microorganisms. In the present study, the sustainable synthesis and characterization of biocompatible silver nanoparticles (AgNPs) from leaf extracts of Semecarpus anacardium, Glochidion lanceolarium, and Bridelia retusa was explored. Continuous synthesis was observed in a UV-vis spectroscopic analysis and the participating phytoconstituents, flavonoids, phenolic compounds, phytosterols, and glycosides, were characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy. The size and surface charge of the particles were also measured by dynamic light scattering spectroscopy. Scanning electron microscopy study was employed to examine the morphology of the nanoparticles. The spectroscopic and microscopic study confirmed the successful synthesis of AgNPs by plant extracts acting as strong reducing agents. The synthesized AgNPs were screened for antibacterial and anti-biofilm activity against human pathogens Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Results of the study demonstrate the potential of phyto-synthesized AgNPs to act as anti-biofilm agents and for other biomedical applications.

Nutritional assessment study and role of green silver nanoparticles in shelf-life of coconut endosperm to develop as functional food.

Tender coconut water is a pure and nutritious drink which play important role as nutraceuticals and pharmaceuticals contributes to the rapid growth of the functional food industry. In the mean-time the safety and shelf-life of the food is crucial for the both product as well as consumers. The intervention or application of nanotechnology gives immense a solution for the prolonged sustainability of the food products. This work reports on the nature of physiological changes of coconut liquid endosperm along with the interaction of its DNA with green route synthesized Ag nanoparticles (AgNPs) using Garuga pinnata leaf, an important ethnomedicinal plant. The physical and nutritional study of the coconut water were carried by UV-visible, XRD, NMR analysis whereas the synthesized Ag nanoparticles (AgNPs) were characterized by UV-Visible spectrophotometer, Raman Spectroscopy, DLS, AFM and FE-SEM analysis. The pH of the endosperm was found to decrease from 6.31 to 4.01, following an exponential decay trend and giving a decay constant of ~8.8 h. The broad absorption peak at ~310 nm gradually turns featureless with elapse of time. The proton nuclear magnetic resonance (H1-NMR) spectrum essentially revealed the presence of esters or organic acids, confirming a sudden fall in the rate of intensity in the immature coconut endosperms as compared to the matured coconut cases. While the pentosyl methyl group (~1.4-1.5 ppm) concentration is observably lowered, free amino acid (~1 ppm) is apparently suppressed in the former specimen. Gel electrophoresis of 10 kb DNA with Ag nanoparticles (AgNPs) showed a gradual decrease of band intensity for a concentration varying between 3:1 and 1:1. The less intense band was due to the lack of migration of DNA into the micropores of the gel as a consequence of interaction of negatively charged DNA with negatively charged AgNPs. The study of DNA interaction with AgNPs could help identifying and addressing the nature of degradation process while considering prevention from microbial attack and make the coconut water as potential functional food entity.

Differential antibacterial response exhibited by graphene nanosheets toward gram-positive bacterium Staphylococcus aureus.

Two different morphological forms of graphene nanosheets: improved reduced graphene oxide (IRGO) and modified reduced GO (rGO) (MRGO) have been synthesised by improved and modified methods, respectively. Physical characterisations of these graphene nanosheets were carried out using X-ray diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy. Colloidal stability of these nanosheets toward a selected bacterium (e.g. Staphylococcus aureus) was ascertained by zeta potential. In the present study, the authors for the first time made an attempt to study and compare the potentialities of these two different forms of graphene nanosheets as efficient bactericidal agents. Field-emission scanning electron microscopy and TEM with energy dispersive X-ray spectroscopy (EDAX) studies of IRGO and MRGO have been carried out to explore their underlying mechanism of antibacterial responses through physical as well as chemical interactions with the selected bacterial species.

Silver Nanoparticles Synthesized Using Wild Mushroom Show Potential Antimicrobial Activities against Food Borne Pathogens.

The present study demonstrates an economical and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using the wild mushroom Ganoderma sessiliforme. The synthesis of AgNPs was confirmed and the products characterized by UV-visible spectroscopy, dynamic light scattering spectroscopy and X-ray diffraction analysis. Furthermore, Fourier transform infrared spectroscopy (ATR-FTIR) analysis was performed to identify the viable biomolecules involved in the capping and active stabilization of AgNPs. Moreover, the average sizes and morphologies of AgNPs were analyzed by field emission scanning electron microscopy (FE-SEM). The potential impacts of AgNPs on food safety and control were evaluated by the antimicrobial activity of the synthesized AgNPs against common food-borne bacteria, namely, Escherichia coli, Bacillus subtilis, Streptococcus faecalis, Listeria innocua and Micrococcus luteus. The results of this study revealed that the synthesized AgNPs can be used to control the growth of food-borne pathogens and have potential application in the food packaging industry. Moreover, the AgNPs were evaluated for antioxidant activity (aDPPH), for biocompatibility (L-929, normal fibroblast cells), and for cytotoxic effects on human breast adenosarcoma cells (MCF-7 & MDA-MB231) to highlight their potential for use in a variety of bio-applications.

Phyto-assisted synthesis of bio-functionalised silver nanoparticles and their potential anti-oxidant, anti-microbial and wound healing activities.

Bio- synthesis of silver nanoparticles (AgNPs) was made by using the aqueous leaf extract of Ardisia solanacea. Rapid formation of AgNPs was observed from silver nitrate upon treatment with the aqueous extract of A. solanacea leaf. The formation and stability of the AgNPs in the colloidal solution were monitored by UV-visible spectrophotometer. The mean particle diameter of AgNPs was calculated from the DLS with an average size ∼4 nm and ∼65 nm. ATR-FTIR spectroscopy confirmed the presence of alcohols, aldehydes, flavonoids, phenols and nitro compounds in the leaf which act as the stabilizing agent. Antimicrobial activity of the synthesized AgNPs was performed using agar well diffusion and broth dilution method against the Gram-positive and Gram-negative bacteria. Further, robust anti-oxidative potential was evaluated by DPPH assay. The highest antimicrobial activity of synthesized AgNPs was found against Pseudomonas aeruginosa (28.2 ± 0.52 mm) whereas moderate activity was found against Bacillus subtilis (16.1 ± 0.76), Candida kruseii (13.0 ± 1.0), and Trichophyton mentagrophytes (12.6 ± 1.52). Moreover, the potential wound healing activity was observed against the BJ-5Ta normal fibroblast cell line. Current research revealed that A. solanacea was found to be a suitable source for the green synthesis of silver nanoparticles.

Biogenic synthesis of silver nanoparticles from Cassia fistula (Linn.): In vitro assessment of their antioxidant, antimicrobial and cytotoxic activities.

The present study reports on biogenic-synthesised silver nanoparticles (AgNPs) derived by treating Ag ions with an extract of Cassia fistula leaf, a popular Indian medicinal plant found in natural habitation. The progress of biogenic synthesis was monitored time to time using a ultraviolet-visible spectroscopy. The effect of phytochemicals present in C. fistula including flavonoids, tannins, phenolic compounds and alkaloids on the homogeneous growth of AgNPs was investigated by Fourier-transform infrared spectroscopy. The dynamic light scattering studies have revealed an average size and surface Zeta potential of the NPs as, -39.5 nm and -21.6 mV, respectively. The potential antibacterial and antifungal activities of the AgNPs were evaluated against Bacillus subtilis, Staphylococcus aureus, Candida kruseii and Trichophyton mentagrophytes. Moreover, their strong antioxidant capability was determined by radical scavenging methods (1,1-diphenyl-2-picryl-hydrazil assay). Furthermore, the AgNPs displayed an effective cytotoxicity against A-431 skin cancer cell line by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, with the inhibitory concentration (IC50) predicted as, 92.2 ± 1.2 µg/ml. The biogenically derived AgNPs could find immense scope as antimicrobial, antioxidant and anticancer agents apart from their potential use in chemical sensors and translational medicine.