Zinc C293 as a novel scaffold with dual activity against HIV-1 integrase and reverse transcriptase.

HIV-1 drug resistance remains a major challenge in antiretroviral therapy, highlighting the need for new and more effective inhibitors. This study explores Zinc C293 as a potential dual inhibitor targeting two key HIV-1 enzymes: integrase (IN) and reverse transcriptase (RT). Initially identified through pharmacophore-based virtual screening, Zinc C293 was further analyzed using molecular docking and molecular dynamics (MD) simulations to understand its stability and interactions with IN.

The gut microbiome: an emerging epicenter of antimicrobial resistance?

The human gut is one of the most densely populated microbial environments, home to trillions of microorganisms that live in harmony with the body. These microbes help with digestion and play key roles in maintaining a balanced immune system and protecting us from harmful pathogens. However, the crowded nature of this ecosystem makes it easier for harmful bacteria to acquire antimicrobial resistance (AMR) genes, which can lead to multidrug-resistant (MDR) infections.

A critical review on and models for the investigation of infection.

is a stomach-dwelling bacterium with a crude global prevalence of nearly 45% in adults and 35% in children and adolescents. Chronic infection and the resulting inflammation are major causes of gastritis, peptic ulcer disease and gastric cancer. Since its discovery in 1982, various animal models have been proposed to recreate the specific pathophysiological interactions between and the human host.

PqsR-specific quorum sensing inhibitors targeting : current advances and future directions.

The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa is driven by diverse resistance mechanisms, including quorum sensing (QS) and biofilm formation. QS regulates virulence, antibiotic tolerance, efflux pumps, and biofilm development, enhancing the pathogen's adaptability. Among QS systems, the Pseudomonas quinolone signal regulator (PqsR) plays a central role in controlling virulence and biofilm-associated genes.

Exploring daidzein dimethyl ether from Albizzia lebbeck as a novel quorum sensing inhibitor against Pseudomonas aeruginosa: Insights from in vitro and in vivo studies.

Infections of multidrug-resistant pathogens including Pseudomonas aeruginosa, cause a high risk of mortality in immunocompromised patients and underscore the need for novel natural antibacterial drugs. In this study, common phytochemicals prevalent in fruits and vegetables have been demonstrated for their ability to inhibit quorum sensing (QS) in Pseudomonas aeruginosa PAO1 (PA). Ten compounds were screened virtually by molecular docking, among which, daidzein dimethyl ether originally from Albizzia lebbeck showed the most significant inhibitory effect on the formation of biofilm and the accumulation of virulence factors, including elastase, pyocyanin and rhamnolipid in PA.

Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3'-Processing Suppression.

: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3'-processing (3'P), thereby establishing its dual-targeting capability.

"Extracellular Vesicle DNA: Advances and Applications as a Non-Invasive Biomarker in Disease Diagnosis and Treatment".

Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures released by cells into the extracellular milieu. These vesicles encapsulate a diverse array of molecular constituents, including nucleic acids, proteins, and lipids, which provide insights into the physiological or pathological conditions of their parent cells. Despite their potential, the study of EV-derived DNA (EV-DNA) has gathered relatively limited attention.

Repurposing Plant-Based Histone Acetyltransferase Inhibitors: A Review of Novel Therapeutic Strategies Against Drug-Resistant Fungal Biofilms.

The rapid emergence of drug-resistant fungal strains necessitates the development of novel therapeutic approaches for battling biofilm-related infections. Biofilms, efflux pumps, and suppression of virulence traits in pathogenic yeasts are governed by epigenetic enzymes, namely, histone acetyltransferases (HATs) and histone deacetylases (HDACs). The review article is focused on the use of histone acetyltransferase inhibitors (HATi), a mechanism-based epidrug that inactivates the regular function of HATs.

Dipeptides from Lactiplantibacillus plantarum limit Pseudomonas aeruginosa pathogenesis.

Aims: Lactobacilli have drawn a great deal of attention due to the heterogeneity of their cells, as well as their remarkable ability to adapt to a range of harsh conditions. One such adaptation response by Lactiplantibacillus plantarum was forming a V-shaped cell structure in low acidic pH conditions. This study aims to identify low pH induced-biofilm formation in L.

Synergy of histone acetyltransferase inhibitor (HATi) with quercetin inhibits biofilm formation in Candida tropicalis.

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid (AA), and quercetin, a known flavonoid, significantly prevented biofilm formation by C.

Repurposing methuosis-inducing anticancer drugs for anthelmintic therapy.

Drug-resistant parasitic nematodes pose a grave threat to plants, animals, and humans. An innovative paradigm for treating parasitic nematodes is emphasized in this opinion. This approach relies on repurposing methuosis (a death characterized by accumulation of large vacuoles) inducing anticancer drugs as anthelmintics.

Precise genome engineering in Pseudomonas using phage-encoded homologous recombination and the Cascade-Cas3 system.

A lack of generic and effective genetic manipulation methods for Pseudomonas has restricted fundamental research and utilization of this genus for biotechnology applications. Phage-encoded homologous recombination (PEHR) is an efficient tool for bacterial genome engineering. This PEHR system is based on a lambda Red-like operon (BAS) from Pseudomonas aeruginosa phage Ab31 and a Rac bacteriophage RecET-like operon (Rec-TE) from P.

Effects of Phytic Acid-Degrading Bacteria on Mineral Element Content in Mice.

Trace minerals are extremely important for balanced nutrition, growth, and development in animals and humans. Phytic acid chelation promotes the use of probiotics in nutrition. The phytic acid-degrading strain psm16 was obtained from swine milk by enrichment culture and direct plate methods.

Saccharochelins A-H, Cytotoxic Amphiphilic Siderophores from the Rare Marine Actinomycete sp. D09.

Siderophores are secreted by microorganisms to survive in iron-depleted conditions, and they also possess tremendous therapeutic potential. Genomic-inspired isolation facilitated the identification of eight amphiphilic siderophores, saccharochelins A-H (-), from a rare marine-derived species. Saccharochelins feature a series of fatty acyl groups appended to the same tetrapeptide skeleton.

Recombineering facilitates the discovery of natural product biosynthetic pathways in Pseudomonas parafulva.

Microbial natural products among other functions they play a vital role in the disease prevention in humans, animals and plants. Pseudomonas parafulva CRS01-1 is a broad-spectrum antagonistic bacterium present in plants. However, no natural products have been isolated from this strain till date.

Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines.

Trillions of bacteria reside in the human gut and they metabolize dietary substances to obtain nutrients and energy while producing metabolites. Therefore, different dietary components could affect human health in various ways through microbial metabolism. Many such metabolites have been shown to affect human physiological activities, including short-chain fatty acids metabolized from carbohydrates; indole, kynurenic acid and para-cresol, metabolized from amino acids; conjugated linoleic acid and linoleic acid, metabolized from lipids.

Attenuation of Quorum Sensing by Natural Products: Virtual Screening, Evaluation and Biomolecular Interactions.

Natural products play vital roles against infectious diseases since ancient times and most drugs in use today are derived from natural sources. Worldwide, multi-drug resistance becomes a massive threat to the society with increasing mortality. Hence, it is very crucial to identify alternate strategies to control these 'super bugs'.

Biosynthesis of polyketides by -AT polyketide synthases in Burkholderiales.

Widely used as drugs and agrochemicals, polyketides are a family of bioactive natural products, with diverse structures and functions. Polyketides are produced by megaenzymes termed as polyketide synthases (PKSs). PKS biosynthetic pathways are divided into the -AT PKSs and -AT PKSs; a division based mainly on the absence of an acyltransferase (AT) domain in the AT PKS modules.

Molecular docking and biological evaluation of novel urea-tailed mannich base against Pseudomonas aeruginosa.

Emergence of multi-drug resistant bacterial pathogens is escalating and it is essential to develop novel strategies to combat these super bugs. LasR is a regulator switch that plays a vital role in quorum sensing (QS) and pathogenesis of Pseudomonas aeruginosa. The present study reports two novel Mannich base (1-(phenyl (o-tolylamino) methyl) urea and 3-((1H-Imidazole-1-yl) methylnaphthalene-2-ol with enhanced anti-QS and antibiofilm activities.

Nematicidal and insecticidal activities of halogenated indoles.

Parasite death via ion channel activations is the hallmark of anthelmintic and antiparasitic drugs. Glutamate gated chloride channel (GluCl) is a prominent targets for drug selection and design in parasitology. We report several iodine-fluorine based lead activators of GluCl by computational studies and structure-activity relationship analysis.

Molecular docking and ADME properties of bioactive molecules against human acid-beta-glucosidase enzyme, cause of Gaucher's disease.

Gaucher disease is one of the common lysosomal storage diseases widespread all over the world. It is divided into three types such as type 1 (non-neuropathic), type 2 (acute infantile neuropathic) and type 3 (chronic neuropathic). This is caused by the deficiency of glucocerebrosidases from the midpoint nervous system.

Engineering Pseudomonas protegens Pf-5 to improve its antifungal activity and nitrogen fixation.

In agricultural production, sustainability is currently one of the most significant concerns. The genetic modification of plant growth-promoting rhizobacteria may provide a novel way to use natural bacteria as microbial inoculants. In this study, the root-colonizing strain Pseudomonas protegens Pf-5 was genetically modified to act as a biocontrol agent and biofertilizer with biological nitrogen fixation activity.

Natural Products from Mammalian Gut Microbiota.

The mammalian gut has a remarkable abundance of microbes. These microbes have strong potential to biosynthesize distinct metabolites that are promising drugs, and many more bioactive compounds have yet to be explored as potential drug candidates. These small bioactive molecules often mediate important host-microbe and microbe-microbe interactions.

Mannich base limits Candida albicans virulence by inactivating Ras-cAMP-PKA pathway.

Mannich bases and its derivatives are regarded as supreme pharmacophores in therapeutics. The study investigates the antimycotic potential of Mannich bases, 1-((1H-benzimidazol-1-yl) methyl) urea (C1) and 1-((3-hydroxynapthalen-2-yl) methyl) thiourea (C2), against Candida albicans. Biofilm and hyphal inhibitory activities of the Mannich bases were tested by crystal violet quantification, fluorescence imaging cAMP rescue, qRT PCR, and by molecular docking analysis.

Virtual Screening and Biomolecular Interactions of CviR-Based Quorum Sensing Inhibitors Against .

The rise of bacterial multi drug resistance becomes a global threat to the mankind. Therefore it is essential to find out alternate strategies to fight against these "super bugs." Quorum sensing (QS) is a cell-to-cell communication mechanism by which many bacteria regulate their biofilm and virulence factors expression to execute their pathogenesis.