Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus’s ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from −7.4 to −8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from −6.2 to −8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical

Modified coptisine derivatives as an inhibitor against pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg virus by molecular docking and molecular dynamics simulation-based drug design approach

During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses

Exploring the nutritional and health benefits of pulses from the Indian Himalayan region: A glimpse into the region’s rich agricultural heritage

Pulses have been consumed worldwide for over 10 centuries and are currently among the most widely used foods. They are not economically important, but also nutritionally beneficial as they constitute a good source of protein, fibre, vitamins and minerals such as iron, zinc, folate and magnesium. Pulses, but particularly species such as Macrotyloma uniflorum, Phaseolus vulgaris L., Glycine max L. and Vigna umbellate, are essential ingredients of the local diet in the Indian Himalayan Region (IHR). Consuming pulses can have a favourable effect on cardiovascular health as they improve serum lipid profiles, reduce blood pressure, decrease platelet activity, regulate blood glucose and insulin levels, and reduce inflammation. Although pulses also contain anti-nutritional compounds such as phytates, lectins or enzyme inhibitors, their deleterious effects can be lessened by using effective processing and cooking methods. Despite their great potential, however, the use of some pulses is confined to IHR regions. This comprehensive review discusses the state of the art in available knowledge about various types of pulses grown in IHR in terms of chemical and nutritional properties, health effects, accessibility, and agricultural productivity.Universidade de Vigo/CISU

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus

Exosomes in liquid biopsy and oncology: Nanotechnological interplay and the quest to overcome cancer drug resistance

Exosomes, small extracellular vesicles of endocytic origin, have emerged as pivotal mediators in intercellular communication, driving transformative advancements across diverse fields of biology and medicine. This comprehensive review delves into the multifaceted roles of exosomes in health and disease, elucidating their biogenesis, cargo composition, and far-reaching implications. Exosomes, secreted by virtually all cell types, encapsulate a cargo comprising proteins, lipids, and nucleic acids, reflecting their cellular origin. Their molecular cargo modulates cellular processes, facilitating complex signalling cascades and contributing to the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and infectious diseases. In cancer, exosomes serve as messengers of tumorigenesis and metastasis, orchestrating critical events within the tumor micro environment. Furthermore, exosomes participate in drug resistance mechanisms, presenting significant challenges in cancer therapy. The diagnostic potential of exosomes, particularly in the context of liquid biopsy, is underscored by their presence in various biofluids. This offers non-invasive disease monitoring and biomarker discovery, revolutionizing early detection and monitoring strategies. Additionally, exosomes have gained recognition as therapeutic vehicles, holding promise for targeted drug delivery, immunomodulation, and regenerative medicine. This review comprehensively explores the ever-expanding landscape of exosome biology, emphasizing their roles in health and disease. It underscores the transformative potential of exosomes in liquid biopsy-based diagnostics and therapeutics while acknowledging the complexities and challenges that lie ahead in harnessing their full clinical utility.</p

Revolutionizing human papillomavirus (HPV)‐related cancer therapies: unveiling the promise of proteolysis targeting chimeras (PROTACs) and proteolysis targeting antibodies (PROTABs) in cancer nano‐vaccines

Personalized cancer immunotherapies, combined with nanotechnology (nano‐ vaccines), are revolutionizing cancer treatment strategies, explicitly targeting Human papilloma virus (HPV)‐related cancers. Despite the availability of preventive vaccines, HPV‐related cancers remain a global concern. Personalized cancer nano‐vaccines, tailored to an individual's tumor genetic mutations, offer a unique and promising solution. Nanotechnology plays a critical role in these vaccines by efficiently delivering tumor‐specific antigens, enhancing immune responses, and paving the way for precise and targeted therapies. Recent advancements in preclinical models have demonstrated the potential of polymeric nanoparticles and high‐density lipoprotein‐mimicking nano‐discs in augmenting the efficacy of personalized cancer vaccines. However, challenges related to optimizing the nano‐carrier system and ensuring safety in human trials persist. Excitingly, the integration of nanotechnology with Proteolysis‐ Targeting Chimeras (PROTACs) provides an additional avenue to enhance the effectiveness of personalized cancer treatment. PROTACs selectively degrade disease‐causing proteins, amplifying the impact of nanotechnology‐based therapies. Overcoming these challenges and leveraging the synergistic potential of nanotechnology, PROTACs, and Proteolysis‐Targeting Antibodies hold great promise in pursuing novel and effective therapeutic solutions for individuals affected by HPV‐related cancers.</p

Targeted therapies for HPV‐associated cervical cancer: harnessing the potential of exosome‐based chipsets in combating leukemia and HPV‐mediated cervical cancer

Exosomes play a crucial role in intercellular communication and have emerged as significant vehicles for transporting disease‐specific biomarkers. This feature provides profound insights into the progression of diseases and the responses of patients to treatments. For example, in leukemia, exosomes convey critical information through the carriage of specific proteins and nucleic acids. In the case of human papillomavirus (HPV)‐mediated cervical cancer, exosomes are particularly useful for noninvasive detection as they transport high‐risk HPV DNA and specific biomolecules, which can be indicators of the disease. Despite their vast potential, there are several challenges associated with the use of exosomes in medical diagnostics. These include their inherent heterogeneity, the need for enhanced sensitivity in detection methods, the establishment of standardization protocols, and the requirement for cost‐effective scalability in their application. Addressing these challenges is crucial for the effective implementation of exosome‐based diagnostics. Future research and development are geared towards overcoming these obstacles. Efforts are concentrated on refining the processes of biomarker discovery, establishing comprehensive regulatory frameworks, developing convenient point‐of‐care devices, exploring methods for multimodal detection, and conducting extensive clinical trials. The ultimate goal of these efforts is to inaugurate a new era of precision diagnostics within healthcare. This would significantly improve patient outcomes and reduce the burden of diseases such as leukemia and HPV‐mediated cervical cancer. The integration of exosomes with cutting‐edge technology holds the promise of significantly reinforcing the foundations of healthcare, leading to enhanced diagnostic accuracy, better disease monitoring, and more personalized therapeutic approaches.</p

Structural and Functional Characterization at the Molecular Level of the MATE Gene Family in Wheat in Silico

A series of multidrug extransporters known as the multidrug and potentially toxic extrusion (MATE) genes are found in all living things and are crucial for the removal of heavy metal ions, metalloids, exogenous xenobiotics, endogenous secondary metabolites, and other toxic substances from the cells. However, there has only been a small amount of them in silico analysis of the MATE family of genes in plant species. In the current study, the MATE gene family was characterized in silico where two families and seven subfamilies based on their evolutionary relationships were proposed. Plant breeders may use TraesCS1D02G030400, TraesCS4B02G244400, and TraesCS1A02G029900 genes for marker-assisted or transgenic breeding to develop novel cultivars since these genes have been hypothesized from protein-protein interaction study to play a critical role in the transport of toxic chemicals across cells. The exon number varies from 01 to 14. One exon has TraesCS1A02G188100, TraesCS5B02G562500, TraesCS6A02G256400, and TraesCS6D02G384300 genes, while 14 exons have only two genes that are TraesCS6A02G418800 and TraesCS6D02G407900. Biological stress (infestations of disease) affects the expression of most of the MATE genes, with the gene TraesCS5D02G355500 having the highest expression level in the wheat expression browser tool. Using the Grain interpretation search engine tool, it is found that the vast bulk of MATE genes are voiced throughout biotic environmental stresses caused by disease pests, with the genotype TraesCS5B02G326600.1 from family 1 exhibiting the greatest level of expression throughout Fusarium head blight infection by Fusarium graminearum after 4 days of infection. The researchers constructed 39 ternary plots, each with a distinct degree of expression under biotic and abiotic stress settings, and observed that 44% of the triplets have imbalanced outputs (extreme values) due to their higher tissue specificity and increased intensity.Peer reviewe

Revolutionizing cancer treatment: The promising horizon of zein nanosystems

ABSTRACT: Various nanomaterials have recently become fascinating tools in cancer diagnostic applications because of their multifunctional and inherent molecular characteristics that support efficient diagnosis and image-guided therapy. Zein nanoparticles are a protein derived from maize. It belongs to the class of prolamins possessing a spherical structure with conformational properties similar to those of conventional globular proteins like ribonuclease and insulin. Zein nanoparticles have gained massive interest over the past couple of years owing to their natural hydrophilicity, ease of functionalization, biodegradability, and biocompatibility, thereby improving oral bioavailability, nanoparticle targeting, and prolonged drug administration. Thus, zein nanoparticles are becoming a promising candidate for precision cancer drug delivery. This review highlights the clinical significance of applying zein nanosystems for cancer theragnostic- moreover, the role of zein nanosystems for cancer drug delivery, anticancer agents, and gene therapy. Finally, the difficulties and potential uses of these NPs in cancer treatment and detection are discussed. This review will pave the way for researchers to develop theranostic strategies for precision medicine utilizing zein nanosystems</p

Plant-derived selenium nanoparticles: investigating unique morphologies, enhancing therapeutic uses, and leading the way in tailored medical treatments

Selenium (Se) is a paramount micronutrient, indispensable for the holistic health of humans, animals, and microorganisms. At its core, Se is instrumental for the genesis of selenocysteine, an exclusive amino acid vital for the assembly of selenoproteins, critical factors in human physiology. While the health dividends of Se are profound, its therapeutic potential is intricately tethered to a precise dosage window, underlining the imperativeness of meticulous calibration. Emerging from this backdrop, selenium nanoparticles (SeNPs) have become the gold standard in nanomaterials, distinguished by their unparalleled immunomodulatory prowess, superior biocompatibility, and enhanced bioavailability. Their reduced toxicity further consolidates their preeminence in biomedical applications. Synthesis methodologies for SeNPs span a spectrum from physical and chemical to biological approaches. Yet, it is the phyto-synthesized SeNPs that reign supreme, characterized by their singular morphological and biochemical attributes, which impart an unmatched compatibility with human tissues. Strikingly, despite their evident superiority, plant-derived SeNPs remain conspicuously underrepresented in the pharmaceutical arena. Contemporary research not only extols the therapeutic potency of SeNPs but also underscores their formidable efficacy against formidable adversaries like cancer cells, microbial pathogens, and viral threats, as well as their robust antioxidant capabilities. This review embarks on a rigorous exposition of the vanguard in plant-mediated SeNPs synthesis, traversing the diverse botanical landscape. It further ventures into the frontier of SeNPs functionalization, illuminating prospects for precision-targeted drug delivery. Conclusively, the review furnishes a comprehensive elucidation of the intricate therapeutic mechanisms harnessed by SeNPs, charting a blueprint for the future of personalized medical interventions.</p