Ribosomal Incorporation of Fluorosulfonyloxy--Phenylalanine into Macrocyclic Peptides for De Novo Target-Specific Covalent Binders.

Macrocyclic peptides are emerging as a promising molecular framework in covalent drug development due to their high specificity, affinity, and low toxicity, addressing challenges such as off-target effects and nonspecific binding associated with traditional covalent binders. Although mRNA display technology has advanced the discovery of covalent peptide binders, it has primarily focused on cysteine residues, thereby limiting the diversity of targetable proteins. In this study, we ribosomally incorporated 4-fluorosulfonyloxy-l-phenylalanine (FSY) into macrocyclic peptides, enabling the construction of a diverse covalent macrocyclic peptide library for de novo screening against human α-thrombin and fibroblast activation protein.

Nanoparticle-based detection of foodborne pathogens: Addressing matrix challenges, advances, and future perspectives in food safety.

Foodborne diseases pose significant public health and economic challenges worldwide, with conventional pathogen detection methods, such as culture-based assays and PCR, often hindered by the complex food matrix in categories like dairy, seafood, fresh produce, and processed foods. These matrices, containing fats, proteins, biofilms, and salts, interfere with detection accuracy, reducing the sensitivity and robustness of traditional approaches. Nanoparticle-based detection systems have emerged as transformative tools to overcome these challenges, offering enhanced sensitivity, rapid detection, and adaptability to real-time monitoring.

A dual-function probe for inhibition and rapid detection of .

We introduce a dual-purpose solvatochromic naphthalimide-benzothiazinone (BTZ) conjugate with theranostic potential that enables specific and rapid detection of by targeting the DprE1 enzyme, while also exhibiting antimicrobial activity. The photoinduced electron transfer (PeT)-based fluorophore incorporates into the mycobacterial cell wall, producing detectable fluorescence within 15 minutes and thus, highlighting its suitability for rapid, point-of-care TB detection in low-resource settings.

i-DENV: development of QSAR based regression models for predicting inhibitors targeting non-structural (NS) proteins of dengue virus.

Introduction: Dengue virus (DENV) is a significant global arboviral threat with fatal potential, currently lacking effective antiviral treatments or a universally applicable vaccine. In response to this unmet need, we developed the "i-DENV" web server to facilitate structure-based drug prediction targeting key viral proteins.

Methods: The i-DENV platform focuses on the NS3 protease and NS5 polymerase of DENV using machine learning techniques (MLTs) and quantitative structure-activity relationship (QSAR) modeling.

Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis.

Diabetes, especially type 2 diabetic mellitus (T2DM) is associated with increased risk of contracting tuberculosis (TB). Though several factors, including immune system dysfunction, have been linked to this sensitivity the exact reasons have yet to be fully elucidated. Although metformin, a diabetic medication, has been suggested as a potential supplementary for host-directed therapy of tuberculosis, the mechanisms of its anti-TB effects remain unclear.

Impact of IMT-P8 on the Efficacy of Conventional Antibiotics for the Treatment of Drug-Resistant and Intracellular .

Addressing the issue of antimicrobial resistance is of the utmost importance on a global scale. We are in dire need of innovative methods and alternatives to new antibiotic discovery in order to address the growing problem of antimicrobial resistance. In this study, we investigated the efficacy of cell-penetrating peptide (IMT-P8) as an adjuvant to enhance the activity of conventional antibiotics against multidrug-resistant and intracellular in vitro and in vivo IMT-P8 potentiates various antibiotics belonging to different classes.

Proline-Mediated Enhancement in Evolvability of Disulfide-Rich Peptides for Discovering Protein Binders.

Disulfide-rich peptides (DRPs), particularly those featuring the inhibitor cystine knot (ICK) motif, represent promising scaffolds for developing next-generation protein modulators and therapeutic agents due to their remarkable stability and specificity. However, their inherent structural integrity and lack of structural plasticity significantly limit their evolvability, creating a fundamental bottleneck in engineering novel functionalities. To address this challenge, we developed a novel proline scanning strategy aimed at enhancing the evolvability of the ICK scaffolds.

Identification of SARS-CoV-2-binding lectins on a commercial lectin array.

The Spike glycoprotein of SARS-CoV-2 is the major target for vaccines and therapeutics. Spike glycosylation is critical for ACE2 binding and subsequent viral fusion and entry. Here, we studied lectins for their ability to bind to SARS-CoV-2 Spike glycoprotein and SARS-CoV-2 virions by employing an array of 95 lectins, for 68 of which we predicted glycan-binding specificities using publically available glycan array data and MotifFinder software.

Functional proteomic analysis of Streptomyces sp. F-3 reveals its potential to effectively degrade waste-yeast.

Streptomyces are renowned in pharmaceutical and medical fields for their ability to produce antibiotics and other bioactive secondary metabolites. In order to reduce industrial production costs, it is crucial to find suitable and cheaper raw materials as carbon and nitrogen sources for microbial growth processes. This study investigated the substrate preference of Streptomyces sp.

Chemically Synthesized LRAD3-D1 Interacts with N-Terminal Domain of SARS-CoV-2 Spike Protein.

Growing evidence of post-COVID neurological complications, such as encephalopathy, neurodegeneration, and cognitive impairment, suggests severe acute respiratory syndrome-related corona virus 2 (SARS-CoV-2) viral infection into the central nervous system (CNS). Therefore, understanding the mechanisms of viral entry into the CNS, where human angiotensin-converting enzyme 2 (ACE2) is barely expressed, is critical for addressing the neurological consequences of COVID-19. Importantly, the low-density lipoprotein receptor class A domain containing 3 (LRAD3) is overexpressed in brain cells, suggesting a possible ACE2-independent alternate pathway of viral entry into brain cells.

Combining synthetic biology with synthetic electrochemistry to expand the chemical space of the indolocarbazole family.

Indolocarbazoles, a class of highly privileged scaffolds, hold immense significance in medicinal chemistry due to their diverse biological activities. In this study, we have demonstrated the environmentally benign synthesis of indolocarbazoles by integrating the strengths of synthetic biology and synthetic electrochemistry. Through pathway reconstruction in , a sustained supply of the prototype indolocarbazole k252c (1) was achieved, which could be efficiently -rhamnosylated to produce k252d (2) modular coculture engineering.

Identification of prochlorperazine dimaleate as a Sortase A inhibitor from FDA libraries for MRSA infection treatment.

is acknowledged as an essential contributor to global disease burden, particularly with the emergence of methicillin-resistant (MRSA) and vancomycin-resistant (VRSA) strains. This study employs a systematic computational and experimental strategy to screen and validate FDA-approved drugs to target Sortase A, an essential enzyme involved in MRSA virulence. Herein, we have identified six molecules exhibiting antimicrobial potency against MRSA and reduced biofilm formation.

Targeting MDR Acinetobacter baumannii with phyto-synthesized silver nanoconjugates of Valeriana wallichii: A mechanistic, in-silico, and cytotoxic investigation.

The escalating global crisis of antimicrobial resistance demands urgent attention. This study, prompted by the World Health Organization's 2020 report foreseeing Acinetobacter baumannii (A. baumannii) as a potential source of future epidemics, explores a sustainable solution.

Establishment and improvement of genetic manipulation tools for .

An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases. , a ubiquitous periodontitis-causing bacterium in the oral cavity, is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases, including cancers, cardiovascular diseases, and adverse pregnancy outcomes (APOs). is one of the few oral anaerobes that can be cultured purely and is a 'model species' for studying the impact of oral health on systemic health.

Exploring microbial natural products through NMR-based metabolomics.

Covering: 2000. 01 to 2025. 03The soaring demand for novel drugs has led to an increase in the requirement for smart methods to aid in the exploration of microbial natural products (NPs).

Microplastic contamination in fish: A systematic global review of trends, health risks, and implications for consumer safety.

Microplastic contamination in fish presents a growing environmental and public health concern, with implications that extend from aquatic ecosystems to consumer safety. This review presents a systematic summary of current knowledge about the health hazards of microplastics in fishes, including bioaccumulation, transfer mechanisms in the food chain, and the roles of microplastics as carriers of antibiotic-resistant genes. By comparing the level of contamination in both safely grown mud fish under aquaculture and directly from natural sources such as nearby coastal areas, we are able to point out the fluctuations of the risks of being contaminated from the different sources for a common consumer and suitable bodies to take action on which type of seafood should be preferred.

Genome wide analysis of Priestia aryabhattai_OP, an endobacterium, modulating growth, development and biochemical compositions of sporophores in edible oyster mushroom Pleurotus ostreatus (MTCC 1802).

The increasing global interest in the consuming and producing of edible oyster mushrooms (Pleurotus spp.) is driven by their well-documented nutritional and health benefits. The metagenomic analysis of fruiting body revealed a distinct microbial composition in P.

Anti-EBV: Artificial intelligence driven predictive modeling for repurposing drugs as potential antivirals against Epstein-Barr virus.

Epstein-Barr virus (EBV) is linked to various cancers like gastric carcinoma, nasopharyngeal carcinoma, and Burkitt's lymphoma, leading to around 200,000 deaths annually. Despite efforts, FDA-approved drugs to combat EBV infection are lacking. In this endeavor, we have developed an AI/ML based predictive algorithm "Anti-EBV" to find potential antivirals against EBV.

Vetiver, (L.) Nash: Biotechnology, Biorefineries, and the Production of Volatile Phytochemicals.

This current review study covers the applications of vetiver essential oil (VEO) in phytoremediation, emphasizing its remedial capabilities in the cleaning of environmental pollutants like pesticides, fertilizers, fungicides, herbicides, heavy metals, dyes, and other industrial wastes such as chemical, mining, pharmaceutical, and other radioactive wastes. The review also emphasizes the pharmacological potential of vetiver essential oil for different applications, such as antioxidant, anti-inflammatory, antifungal, antibacterial, antitubercular, antihyperglycemic, antidepressant, hepatoprotective, and nephroprotective uses. The commercial potential of vetiver essential oil in diverse sectors, including global perspectives, is also illustrated along with demand scenarios in different sectors like food, beverage, fragrance, cosmetic and aromatherapy, hygiene, and pharmaceutical sectors.

Ribosomal incorporation of -acetyl-3,5-bis(chloromethyl)benzylthio-L-alanine for developing an mRNA-displayed bicyclic peptide library cyclized 1,3,5-tris(methyl)benzene.

We report a novel method for constructing an mRNA-displayed bicyclic peptide library cyclized through 1,3,5-tris(methyl)benzene by ribosomally incorporating -acetyl-3,5-bis(chloromethyl)benzylthio-L-alanine, enabling the selection of bicyclic peptides against specific targets. Using this method, we successfully identified bicyclic peptides that bind to human Trop2 and VEGF165, providing a new strategy for selecting bicyclic peptides cyclized by trimethylbenzene.

Microbial degradation and pollutant control in aerobic composting and anaerobic digestion of organic wastes: A review.

Aerobic composting (AC) and anaerobic digestion (AD) are promising technologies for organic waste treatment, but their efficiency and safety are influenced by complex waste composition and persistent contaminants. This review identifies the advances in understanding microbial community dynamics, enzymatic degradation pathways, and the fate of contaminants during AC and AD processes. The findings indicate that substrate composition shapes dominant microbial populations and their degradative enzymes, with this correlation potentially useful for predicting functional microbial communities.

Programming virulent bacteriophages by developing a multiplex genome engineering method.

Unlabelled: The use of virulent bacteriophages (phages) against pathogenic bacteria has recently attracted considerable interest. The limitations of naturally isolated phages have promoted the development of genome engineering methods to optimize their functions; however, engineering of virulent phage genomes in bacterial hosts remains challenging. Here, we describe a SMART (plitting, odifying, ssembling, and ebooing) method for multiplex genome engineering of virulent phages by plitting the genome into multiple segments cloned and inserted into single-copy bacterial artificial chromosome vectors in to overcome the toxicity of phage gene products, odifying multiple targeted loci in parallel through recombineering, ssembling split segments into an intact genome, and ebooing the recombined phage in bacterial hosts.

Investigating the role of polar amino acids driven by evolution in the active site architecture of GH11 xylanase.

Enzymes, as vital biomacromolecules, have developed significant plasticity, enabling adaptation to diverse environments and catalysis of numerous biochemical reactions. However, enzyme evolution is constrained by mutational limitations, as amino acid substitutions often impair structure or function, hampering optimization endeavors. To address this, we integrated structural bioinformatics with site-directed mutagenesis to investigate the evolutionary trends of four GH11 family xylanases (XynA, XynB, XynD, and XynE) from Aspergillus niger An76.

Genomic insights into novel predatory myxobacteria isolated from human feces.

Myxobacteria are Gram-negative, spore-forming predatory bacteria isolated from diverse environmental samples that feed on other microbes for their survival and growth. However, no reports of cultured representatives from the human gut have been published to date, although previous investigations have revealed the presence of myxobacterial operational taxonomic units (OTUs) in skin and fecal samples. In this study, three myxobacterial strains designated as O35, O15, and Y35 were isolated and purified from fecal samples of two inflammatory bowel disease (IBD) patients.