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The current pandemic Covid-19 brought about by a newly emerged and highly infectious virus named as Sars-CoV-2 as a worldwide danger, has infected more than 600 million people and number of deaths are continuously rising day by day. Till date there are no medications accessible for treatment. All over the world scientists and researchers are involved in the study of this emerged virus and its lifecycle. Structures of proteins in the life cycle of virus has been revealed in RCSB PDB (Research Collaboratory for Structural Bioinformatics Protein Data Bank) by researchers. Citrus fruits are used to treat many distresses of humans. Literature survey shows that it has various activities. Our research work is meant to identify the phytoconstituents which are having phenolic composition and good antiviral and antioxidant properties from citrus fruits against Covid-19 proteins (spike binding domain with ACE2 receptor and spike binding domain with Main protease) and to know its in-silico molecular basis. In this study, about 25 compounds from citrus fruits which is having a good antiviral and antioxidant properties and also phenolic composition were employed for molecular docking analysis, molecular dynamic simulation studies and ADME studies. Based on present study 2 compounds from Citrus fruits acted well against the Covid-19 proteins. The MD simulations were employed to identify Hesperidin and Procyanidin B2 as hit compounds. Further ADME analysis were studied for top 2 compounds, these compounds can be further taken for in-vitro studies to know the effective activity against Covid-19. HIGHLIGHTS Citrus fruit phytochemicals are fascinating core, which shows an excellent anti-viral, anti-inflammatory and antioxidant properties The SARS-CoV-2 is newly emerged and highly infectious virus, has infected more than 600 million people and number of deaths are continuously rising day by day Molecular docking analysis, Molecular dynamics simulation ADME studies was carried out Compound Hesperidin and Procyanidin B2 showed a good inhibitory activity against SARS-CoV-2 proteins GRAPHICAL ABSTRACT

In the current scenario, nanoparticle synthesis has been fascinated by biogenic approaches than the chemical methods. However, reproducibility of the source stands essentially in nanoparticle synthesis. Nanoparticle synthesis by fungi has more advantages such as the potential for bioaccumulation, immunity towards toxicity, relatively easier to handle, simpler in synthesis and downstream processing. In this study, biogenic copper nanoparticles (CuNPs) were embedded within graphene oxide-chitosan (GO-CS) polymer to endure the biocompatibility and toxicological effects on both normal and cancer cells. The characteristics of the copper nanoparticles/graphene oxide-chitosan (CuNPs/GO-CS) nanocomposites was found to be superior to the GO-CS. This is evident from the results obtained from X-ray diffraction technique, UV-visible spectroscopy, atomic force microscope, fourier transform infrared spectroscopy, fluorescence spectroscopy, confocal laser scanning microscope and scanning electron microscopy. The synthesized new copper nanoparticles/graphene oxide-chitosan (CuNPs/GO-CS) nanocomposites were studied for their anti-bacterial activity against Escherichia coli MTCC 443 and anti-cancer activity on breast cancer MCF7 cell lines.

Prolonged cancer cell survival, acquiring drug resistance, and secondary cancer development despite chemotherapy are the major challenges during cancer treatment, whose underlying mechanism still remains elusive. In this study, low-doses of chemotherapeutic drugs (LDCD) - doxorubicin (DOX), etoposide (ETOP), and busulfan (BUS) were used to ascertain the effect of residual concentrations of drugs on breast cancer cells. Our results showed that exposure to LDCD caused significant induction of ROS, early signs of apoptosis and accumulation of cells in S and G2-M phases of the cell cycle in MCF-7 and MDA-MB-231 cell lines. Under drug-free recovery conditions, a decrease in the number of apoptotic cells and an increase in the number of colonies formed were observed. Analysis of the molecular mechanism showed lower expression of cleaved products of caspase 3, 9, PARP and occurrence of DNA strand breaks in recovered cells compared to LDCD-treated cells, suggesting incomplete cell death activation and survival of cells with genomic damage after therapeutic insult. Thus, LDCD induces defective apoptosis in cancer cells allowing a small population of cells to escape from cell cycle check points and survive with accumulated genetic damage that could eventually result in secondary cancers that warrants further studies for better therapeutic strategies.

The polymer-cobalt(III) complexes, [Co(bpy)(dien)BPEI]Cl3 · 4H2O (bpy = 2,2'-bipyridine, dien = diethylentriamine, BPEI = branched polyethyleneimine) were synthesized and characterized. The interaction of these complexes with human serum albumin (HSA) and bovine serum albumin (BSA) was investigated under physiological conditions using various physico-chemical techniques. The results reveal that the fluorescence quenching of serum albumins by polymer-cobalt(III) complexes took place through static quenching. The binding of these complexes changed the molecular conformation of the protein considerably. The polymer-cobalt(III) complex with x = 0.365 shows antimicrobial activity against several human pathogens. This complex also induces cytotoxicity against MCF-7 through apoptotic induction. However, further studies are needed to decipher the molecular mode of action of polymer-cobalt(III) complex and for its possible utilization in anticancer therapy.

The interaction of surfactant-cobalt(III) complexes [Co(bpy)(dien)TA](ClO4)3 · 3H2O (1) and [Co(dien)(phen)TA](ClO4)3 · 4H2O (2), where bpy = 2,2'-bipyridine, dien = diethylenetriamine, phen = 1,10-phenanthroline and TA = tetradecylamine with human serum albumin (HSA) under physiological conditions was analyzed using steady state, synchronous, 3D fluorescence, UV/visabsorption and circular dichroism spectroscopic techniques. The results show that these complexes cause the fluorescence quenching of HSA through a static mechanism. The binding constant (Kb ) and number of binding-sites (n) were obtained at different temperatures. The corresponding thermodynamic parameters (∆G°, ∆H° and ∆S°) and Ea were also obtained. According to Forster's non-radiation energy transfer theory, the binding distance (r) between the complexes and HSA were calculated. The results of synchronous and 3D fluorescence spectroscopy indicate that the binding process has changed considerably the polarity around the fluorophores, along with changes in the conformation of the protein. The antimicrobial and anticancer activities of the complexes were tested and the results show that the complexes have good activities against pathogenic microorganisms and cancer cells.

Current prospect of nanobiotechnology involves in the greener synthesis of nanostructured materials particularly noble metal nanoparticles for various biomedical applications. In this study, biologically (Podophyllum hexandrum L.) synthesized crystalline gold nanoparticles (AuNPs) with the size range between 5 and 35 nm were screened for its anticancereous potential against human cervical carcinoma cells (HeLa). Stoichiometric proportion of the reaction mixture and conditions were optimized to attain stable nanoparticles with narrow size range. Different high throughput techniques like transmission electron microscope (TEM), X-ray diffraction (XRD) and UV–vis spectroscopy were adopted for the physio-chemical characterization of AuNPs. Additionally, Fourier transform infrared spectroscopy (FTIR) study revealed that the water soluble fractions present in the plant extract solely influences the reduction of AuNPs. Sublimely, synthesized AuNPs exhibits an effective in vitro anticancer activity against HeLa cells via induction of cell cycle arrest and DNA damage. Furthermore, it was evidenced that AuNPs treated cells are undergone apoptosis through the activation of caspase cascade which subsequently leads to mitochondrial dysfunction. Thereby, this study proves that biogenic colloidal AuNPs can be developed as a promising drug candidature for human cervical cancer therapy.

Now-a-days synthesis and characterization of silver nanoparticles (AgNPs) through biological entity is quite interesting to employ AgNPs for various biomedical applications in general and treatment of cancer in particular. This paper presents the green synthesis of AgNPs using leaf extract of Podophyllum hexandrum Royle and optimized with various parameters such as pH, temperature, reaction time, volume of extract and metal ion concentration for synthesis of AgNPs. TEM, XRD and FTIR were adopted for characterization. The synthesized nanoparticles were found to be spherical shaped with average size of 14 nm. Effects of AgNPs were analyzed against human cervical carcinoma cells by MTT Assay, quantification of ROS, RT-PCR and western blotting techniques. The overall result indicates that AgNPs can selectively inhibit the cellular mechanism of HeLa by DNA damage and caspase mediated cell death. This biological procedure for synthesis of AgNPs and selective inhibition of cancerous cells gives an alternative avenue to treat human cancer effectively.

Several studies have reported the antioxidant activity and potential therapeutic properties of Punica granatum L. (Lythraceae) fruit. Medicinal properties have also been attributed to other parts of P. granatum tree, which are rich in bioactive phytochemicals.To explore the phytochemical characteristics, in vitro and in vivo antioxidant and in vivo antigenotoxic potential of P. granatum leaf extract (PLE).The in vitro antioxidant potential of PLE was assessed by DPPH (1,1-diphenyl-2-picrylhydrazyl), ferric reducing antioxidant power (FRAP). Inhibition of lipid peroxidation (LPO) and the total phenolic content of the samples were also determined. Thirty-six male Swiss albino mice were divided into six groups (six animals each). Group 1 (control) and group 2 mice received vehicle and genotoxin alone, respectively. Groups 3, 4 and 5 were pretreated with PLE (400, 600 and 800 mg/kg body weight, respectively) prior to the administration of genotoxin. Group 6 received highest test dose of PLE. DNA damage in the bone marrow cells, hepatic LPO and antioxidants were recorded.Phytochemical analysis of PLE showed the presence of flavonoids, phenols, phytosterols, tannins and carbohydrates. Aqueous PLE demonstrated free radical scavenging activity, reducing power and inhibition of LPO with the EC₅₀ values of 10.25, 59.88 and 20.05, respectively. A significant protective effect was observed against cyclophosphamide induced DNA damage and inhibition of hepatic LPO with concomitant increase in reduced glutathione (GSH) glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in mice pretreated with PLE.PLE demonstrated a significant antioxidant and antigenotoxic potential and hence can be a potential natural source in health and medicine.

A new series of pendant-type polymer-cobalt(III) complexes, [Co(LL)2(BPEI)Cl](2+), (where BPEI = branched polyethyleneimine, LL = dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (dpqc), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer-metal complexes and calf thymus DNA have been performed by UV-Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer-metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc dpq ip. The analysis of the results suggests that polymer-cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer-cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer-cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC50 concentration.

Ethanopharmacological relevance The seeds of Syzygium cumini , Skeels (Jamun) are extensively used in India for treatment of diabetes and other ailments. Aim of the study The aim of this work was to assess the role of Jamun seed extract (JSE) as a chemoprotective agent against in vivo oxidative stress and genomic damage. Materials and methods Experiments were carried out to evaluate in vitro protective effects of JSE against hydroxyl radical induced damage in pBR322 DNA, and in vivo genomic damage and oxidative stress in mice which received JSE orally for 5 days before exposure to genotoxic carcinogens urethane (URE) and 7,12-dimethyl benz( a )anthracene (DMBA). Results Aqueous and ethanolic extracts of JSE showed significant protective effects against hydroxyl radical induced strand breaks in pBR322 DNA. The in vivo experiments with aqueous JSE showed significant protective effects against chromosomal damage induced by the genotoxic carcinogens URE and DMBA. Biochemical assays registered significant inhibition of hepatic lipid peroxidation and increase in GSH level and activity of GST, SOD and CAT. Conclusion Our findings suggest that JSE can possibly play an important role as a chemopreventive agent against oxidative stress and genomic damage.

Polymer complexes [Cu(dpq)2BPEI](ClO4)2·2H2O (dpq-dipyrido[3,2-d;2′,3′-f]quinoxaline; BPEI-branched polyethyleneimine] with different degrees of copper complex content in the polymer chain (x) were synthesized and characterized by UV-Vis, IR, EPR and elemental analysis methods. Absorption spectroscopy, emission spectroscopy, cyclic voltammetry and circular dichroism techniques were used to investigate the binding nature of these polymer–copper(II) complexes with both CT-DNA and yeast tRNA. These experiments revealed that these the polymer–copper(II) complexes bind to both DNA and RNA by an intercalation mode via ligand dpq into the base pairs of DNA/RNA. The binding constant of the polymer–copper(II) complex increases with the degree of coordination. Furthermore, the anti-microbial effects and in vitro cytotoxicity of one of the polymer copper(II) complexes (x = 0.326) were investigated using the disk diffusion method and MTT assay and AO/EB staining. These results suggests that the polymer–copper(II) complex can be used as an effective therapeutic agent.

Neuronal dysfunction has been extensively studied as a central feature of neurodegenerative tauopathies. However, across neurodegenerative diseases, there is strong evidence for active involvement of immune cells like microglia in driving disease pathophysiology. Here, we demonstrate that tau mRNA and protein are expressed in microglia in human brains and in human induced pluripotent stem cell (iPSC)-derived microglia like cells (iMGLs). Using iMGLs harboring the MAPT IVS10+16 mutation and isogenic controls, we demonstrate that a tau mutation is sufficient to alter microglial transcriptional states. We discovered that MAPT IVS10+16 microglia exhibit cytoskeletal abnormalities, stalled phagocytosis, disrupted TREM2/TYROBP networks, and altered metabolism. Additionally, we found that secretory factors from MAPT IVS10+16 iMGLs impact neuronal health, reducing synaptic density in neurons. Key features observed in vitro were recapitulated in human brain tissue and cerebrospinal fluid from MAPT mutations carriers. Together, our findings that MAPT IVS10+16 drives cell-intrinsic dysfunction in microglia that impacts neuronal health has major implications for development of therapeutic strategies.

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10+16, or p.R406W mutation, and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer’s disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.