Ribonucleic acid (RNA) viruses associated with chronic diseases in humans are major threats to public health causing high mortality globally. The high mutation rate of RNA viruses helps them to escape the immune response and also is responsible for the development of drug resistance. Chronic infections caused by human immunodeficiency virus (HIV) and hepatitis viruses (HBV and HCV) lead to acquired immunodeficiency syndrome (AIDS) and hepatocellular carcinoma respectively, which are one of the major causes of human deaths. Effective preventative measures to limit chronic and re-emerging viral infections are absolutely necessary. Each class of antiviral agents targets a specific stage in the viral life cycle and inhibits them from its development and proliferation. Most often, antiviral drugs target a specific viral protein, therefore only a few broad-spectrum drugs are available. This review will be focused on the selected viral target proteins of pathogenic viruses containing single-stranded (ss) RNA genome that causes chronic infections in humans (e.g. HIV, HCV, Flaviviruses). In the recent past, an exponential increase in the number of available three-dimensional protein structures (>150000 in Protein Data Bank), allowed us to better understand the molecular mechanism of action of protein targets and antivirals. Advancements in the in silico approaches paved the way to design and develop several novels, highly specific small-molecule inhibitors targeting the viral proteins.
: Alzheimer’s disease (AD), a major form of dementia, has been reported to affect more than 50 million people worldwide. It is characterized by the presence of amyloid-β (Aβ) plaques and hyperphosphorylated Tau-associated neurofibrillary tangles in the brain. Apart from AD, microtubule (MT)-associated protein Tau is also involved in other neurodegenerative diseases called tauopathies, including Pick’s disease, frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration. The recently unsuccessful phase III clinical trials related to Aβ-targeted therapeutic drugs indicated that alternative targets, such as Tau, should be studied to discover more effective and safer drugs. Recent drug discovery approaches to reduce AD-related Tau pathologies are primarily based on blocking Tau aggregation, inhibiting Tau phosphorylation, compensating impaired Tau function with MT-stabilizing agents, and targeting the degradation pathways in neuronal cells to degrade Tau protein aggregates. Owing to several limitations of the currently-available Tau-directed drugs, further studies are required to generate further effective and safer Tau-based disease-modifying drugs. Here, we review the studies that focused on medicinal plant-derived compounds capable of modulating the Tau protein, which is significantly elevated and hyperphosphorylated in AD and other tauopathies. We mainly considered the studies that focused on Tau protein as a therapeutic target. We reviewed several pertinent papers retrieved from PubMed and ScienceDirect using relevant keywords, with a primary focus on the Tau-targeting compounds from medicinal plants. These compounds include indolines, phenolics, flavonoids, coumarins, alkaloids, and iridoids, which have been scientifically proven to be Tau-targeting candidates for the treatment of AD.
Opportunistic skin pathogens and their resistance to pre-existing therapeutics are a challenge to normal physiological wound healing processes. Consistent development of antimicrobial agents is required to overcome the complications raised by antimicrobial resistance. An effective alternative proposed in recent research includes the use of antimicrobial nanoparticles or nanobiopolymers. Unfortunately, metallic nanoparticles that have been proven as antimicrobial agents also possess a certain level of toxicity. In this work, we demonstrate the use of a cationic polymer, branched polyethyleneimine (B-PEI), that has been electrospun to obtain a scaffold/fiber (B-PEI NF) mat resulting in a large surface area-to-volume ratio. SEM analysis revealed that the average diameter of the obtained fibers is 240 nm. The formation of nanoscaffold modulates the controlled release of the polymer from the matrix resulting in long-term effects. The antimicrobial and antibiofilm activity of the B-PEI nanofiber (B-PEI NF) was evaluated against ESKAPE pathogens (Pseudomonas aeruginosa and Staphylococcus aureus) and also against Candida albicans. Dose-dependent inhibition was observed for microbial growth and biofilm for all three test organisms, the minimum inhibitory concentration required for inhibiting P. aeruginosa, S. aureus, and C. albicans is 33.125, 26.5, and 19.875 μM, respectively, in 2 mL of bacterial/fungal broth. Crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed significant reduction in biomass and cell viability of sessile cells, respectively, within the biofilm after treatment using B-PEI NFs. A B-PEI NF matrix promotes cell migration and wound healing processes by mimicking the extracellular matrix. In vitro wound healing studies showed a fivefold increase in cell migration and wound healing by B-PEI NFs (97% wound coverage in 17 h) when compared to B-PEI (15% wound coverage in 17 h). The in vitro wound healing assays confirmed the biocompatibility and better wound healing activity of B-PEI NF mats.
Single-stranded DNA (ssDNA) is a prerequisite for electrochemical sensor-based detection of parasite DNA and other diagnostic applications. To achieve this detection, an asymmetric polymerase chain reaction method was optimised. This method facilitates amplification of ssDNA from the human lymphatic filarial parasite Wuchereria bancrofti. This procedure produced ssDNA fragments of 188 bp in a single step when primer pairs (forward and reverse) were used at a 100:1 molar ratio in the presence of double-stranded template DNA. The ssDNA thus produced was suitable for immobilisation as probe onto the surface of an Indium tin oxide electrode and hybridisation in a system for sequence-specific electrochemical detection of W. bancrofti. The hybridisation of the ssDNA probe and target ssDNA led to considerable decreases in both the anodic and the cathodic currents of the system's redox couple compared with the unhybridised DNA and could be detected via cyclic voltammetry. This method is reproducible and avoids many of the difficulties encountered by conventional methods of filarial parasite DNA detection; thus, it has potential in xenomonitoring.
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