Thermal and mechanical properties of high-performance polyester nanobiocomposites reinforced with pre-treated sunn hemp fiber for automotive applications.

The objective of this study is to create high-performance nano biocomposites by utilizing unsaturated polyester resin (PE) reinforced with pre-treated short (2 cm) lengthened sunn hemp (SH) fibers and by incorporating 5 % nanoclay (hydrophilic bentonite) through the compression molding technique. The addition of 5 % nanoclay to the biocomposite significantly increased the flexural strength by approximately 165 % for H2O2-treated SH fiber and 148 % for KMnO4-treated SH fiber, when compared to untreated fibers. This enhancement was achieved through phase separation, intercalation, and exfoliation between the SH fibers, polyester resin (PE), and 5 % nanoclay. In particular, the H2O2-treated SH fiber nanobiocomposite exhibited a 43 % higher flexural strength compared to its corresponding biocomposite. The incorporation of nanoclay significantly decreased the water absorption of the bio-composites from 11.86 % in the untreated samples to a minimum of 2.76 % in the H2O2-treated SH/PE nanobiocomposite. The study suggests that short SH fiber/PE/nanoclay nanobiocomposites could be used as effective alternatives to synthetic composites in various applications, including the aerospace industry, household products, and automotive interior components such as side panels, seat frames, and central consoles. Additionally, they could be utilized in exterior parts like door panels and dashboards.

Immunomodulatory zymosan/ι-carrageenan/ agarose hydrogel for targeting M2 to M1 macrophages (antitumoral).

Several studies have been performed on the immunomodulatory effects of yeast ß-(1,3) glucan, but there is no proper evaluation of the thermal and immunomodulating properties of zymosan (ZM). Thermogravimetry analysis indicated a 54% weight loss of ZM at 270 °C. Circular dichroism showed absorption peaks in the region of 250 to 400 nm, suggesting a helical coil ß-sheet configuration. XRD showed a broad peak at 2θ of 20.38°, indicating the crystalline nature, and the size was found to be 23 nm. ZM is biocompatible and showed no toxicity against L929 and RAW 264.7 cell lines (cell viability > 90%). Immunomodulatory studies with PCR showed upregulation of M1 genes in human differentiated THP-1 macrophage cell lines, which were responsible for antitumor properties. The uptake of ZM particles inside the differentiated THP-1 macrophages and Raw 264.7 cells was confirmed (Video clip). ZM particle uptake via Dectin-1 was identified by competitive receptor blocking. Seaweed derived carrageenan/ZM/agarose hydrogel was successfully prepared (@5 : 5 wt%) and was seen to support the growth of L929 cells (1 × 105 cells per mL) and have a higher swelling (≈250-280%). This study indicates that ZM-based hydrogel could be a potential drug carrier (Rifampicin and Levofloxacin) for targeting tumour-associated macrophages (M2).

In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor.

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10µg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.

Significant perspectives on various viral infections targeted antiviral drugs and vaccines including COVID-19 pandemicity.

A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carriers, nanoemulsions, nanogels, metal based nanoparticles, alike the future nanosystems through nanobubbles, nanofibers, nanodiamonds, nanotraps, nanorobots and eventually, the therapeutic applications of micro- and nanoparticulates, current status for clinical development against COVID-19 together with environmental implications of antivirals, gene therapy etc., which may be useful for repurposing and designing of novel antiviral drugs against various dreadful diseases, especially the SARS-CoV-2 and other associated variants.

Arjunetin as a promising drug candidate against SARS-CoV-2: molecular dynamics simulation studies.

Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, -8.4 kcal/mol; PLpro, -7.6 kcal/mol and RdRp, -8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, -7.2 kcal/mole and PLpro -7.7 kcal/mole) and Remdesivir (RdRp -7.6 kcal/mole). To further investigate this, we performed 200-500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19.Communicated by Ramaswamy H. Sarma.

A comprehensive overview of vaccines developed for pandemic viral pathogens over the past two decades including those in clinical trials for the current novel SARS-CoV-2.

The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavirus namely, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Researchers are working around the clock to control this pandemic and consequent waves of viral reproduction, through repurposing existing drugs as well as designing new vaccines. Several countries have hastened vaccine design and clinical trials to quickly address this outbreak. Currently, more than 250 aspirants against SARS-CoV-2 are in progress, including mRNA-replicating or non-replicating viral vectored-, DNA-, autologous dendritic cell-based-, and inactivated virus-vaccines. Vaccines work by prompting effector mechanisms such as cells/molecules, which target quickly replicating pathogens and neutralize their toxic constituents. Vaccine-stimulated immune effectors include adjuvant, affinity, avidity, affinity maturation, antibodies, antigen-presenting cells, B lymphocytes, carrier protein, CD4+ T-helper cells. In this review, we describe updated information on the various vaccines available over the last two decades, along with recent progress in the ongoing battle developing 63 diverse vaccines against SARS-CoV-2. The inspiration of our effort is to convey the current investigation focus on registered clinical trials (as of January 08, 2021) that satisfy the safety and efficacy criteria of international wide vaccine development.

Mechanical and Water Absorption Properties of Short Banana Fiber/Unsaturated Polyester/Molecular Sieves + ZnO Nanorod Hybrid Nanobiocomposites.

ZnO nanorods were prepared by the sol-gel method and characterized using UV-visible absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis/differential thermogravimetry (TGA/DTG), high-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray spectroscopy (EDAX). Banana fiber/polyester resin (BF/PE) biocomposites and BF/PE/MS/nano ZnO nanobiocomposites were made using the untreated and chemically treated (with NaOH, formic acid, acetic anhydride, hydrogen peroxide, and potassium permanganate) banana fiber (BF), unsaturated polyester resin (PE), molecular sieves (MS), and the prepared ZnO nanorods. The KMnO4, Ac2O, and NaOH treatments enhanced the thermal stability of the nanobiocomposites. Addition of 2% of ZnO nanorods increased the tensile strength of all of the chemically treated BF/PE/MS biocomposites. The chemical treatments alone decreased (NaOH-15.4 MPa; KMnO4-14.5 MPa; H2O2-9.9 MPa; Ac2O-7.9 MPa; HCOOH-6.9 MPa) the compressive strength of the untreated BF/PE/MS biocomposite (25.9 MPa). But the chemical treatment and addition of ZnO nanorods enhanced the compressive strength effectively (48.5, 41.6, 39.4, 37.0, and 34.6 MPa for NaOH, HCOOH, KMnO4, H2O2, and Ac2O treatments, respectively) compared to the untreated BF/PE/MS biocomposites (24.0 MPa). The H2O2 (69.0 MPa) and NaOH (62.9 MPa) treatments enhanced the flexural strength of the untreated BF/PE biocomposites (51.6 MPa). The addition of ZnO nanorods enhanced the flexural strength of all of the chemically treated (except NaOH) BF/PE/MS biocomposites (55.7, 59.4, 79.0, and 67.4 MPa for HCOOH, Ac2O, H2O2, and KMnO4 treatments, respectively). The impact strengths of the biocomposites were enhanced by both chemical treatments and addition of ZnO nanorods. The addition of ZnO nanorods decreased the water absorption of the biocomposites significantly from 24.3% for the untreated to a minimum of 14.5% for the H2O2-treated BF/PE/MS/ZnO nanobiocomposite.

Lipid Flip-Flop-Inducing Antimicrobial Phytochemicals from Gymnema sylvestre are Bacterial Membrane Permeability Enhancers.

An amphiphilic phytochemical fraction isolated from methanol extract of Gymnema sylvestre leaf powder contained six terpenoids, two flavonoids, and one alkaloid that induced rapid flip-flop of fluorescent phospholipid analog in the phosphatidyl choline bilayer. Lipid-flipping activity of the methanol-extracted fraction of G. sylvestre (MEFGS) was dose-dependent and time-dependent with a rate constant k = (12.09 ± 0.94) mg-1 min-1 that was saturable at (40 ± 1) % flipping of the fluorescent lipid analogue. Interactions of MEFGS phytochemicals with large unilamelar vesicles led to time-dependent change in their rounded morphology into irregular shapes, indicating their membrane-destabilizing activity. MEFGS exhibited antibacterial activity on Escherichia coli (MTCC-118), Staphylococcus aureus (MTCC-212), and Pseudomonas aeruginosa (MTCC-1035) with IC50 values 0.5, 0.35, and 0.1 mg/mL, respectively. Phytochemicals in MEFGS increased membrane permeabilization in all three bacteria, as indicated by 23, 17, and 17% increase in the uptake of crystal violet, respectively. MEFGS enhanced membrane damage, resulting in a 3-5 fold increase in leakage of cytosolic ions, 0.5-2 fold increase in leakage of PO4 -, and 15-20% increase in loss of cellular proteins. MEFGS synergistically increased the efficacy of curcumin, amoxillin, ampicillin, and cefotaxime on S. aureus probably by enhancing their permeability into the bacterium. For the first time, our study reveals that phytochemicals from G. sylvestre enhance the permeability of the bacterial plasma membrane by facilitating flip-flop of membrane lipids. Lipid-flipping phytochemicals from G. sylvestre can be used as adjuvant therapeutics to enhance the efficacy of antibacterials by increasing their bioavailability in the target bacteria.