The discovery of penta-peptides inhibiting the activity of the formylglycine-generating enzyme and their potential antibacterial effects against Mycobacterium tuberculosis.

The formylglycine-generating enzyme is a key regulator that converts sulfatase into an active form. Despite its key role in many diseases, enzyme activity inhibitors have not yet been reported. In this study, we investigated penta-peptide ligands for FGE activity inhibition and discovered two hit peptides. In addition, the lead peptides also showed potential antibacterial effects in a Mycobacterium tuberculosis model.

Chemical Probes and Activity-Based Protein Profiling for Cancer Research.

Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are traceable or detectable in tests for cancer diagnosis and treatment. Currently, fluorogenic chemical probes are widely used to detect cancer-associated proteins and their binding partners. These probes are also applicable in photodynamic therapy to determine drug efficacy and monitor regulating factors. In this review, we discuss the synthesis of chemical probes for different cancer types from 2016 to the present time and their application in monitoring the activity of transferases, hydrolases, deacetylases, oxidoreductases, and immune cells. Moreover, we elaborate on their potential roles in photodynamic therapy.

Application of fluorescent turn-on aptamers in RNA studies.

RNA is an intermediate player between DNA transcription and protein translation. RNAs also interact with other macromolecules and metabolites and regulate their fate. The emerging number of RNA identifications expanded new areas of study to determine their applicability and functional analysis. Recently, extensive research has been focused on visualizing RNA in living biological samples and a method has been developed by the evolution of specific fluorophore-binding aptamers through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. Several promising fluorescent turn-on aptamers are currently available, and they can detect RNA-RNA, RNA-protein, ligand binding, small molecule, and metabolite interactions in vitro and under live-cell conditions. Here we review the currently available fluorescent turn-on aptamers and discuss their applicability for analyzing the fate of targeted RNAs in in vitro and in vivo systems.

Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing.

OBJECTIVES: The comprehensive in silico study aims to figure out the most effective aromatic phytochemical ligands among a number from a library, considering their pharmacokinetic efficacies in blocking "angiotensin-converting enzyme 2 (ACE2) receptor-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein" complex formation as part of a target-specific drug designing. MATERIALS AND METHODS: A library of 57 aromatic pharmacophore phytochemical ligands was prepared from where the top five ligands depending on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and quantitative structure-activity relationship (QSAR)-based pharmacokinetic properties were considered. The selected ligands were optimized for commencing molecular docking and dynamic simulation as a complex with the ACE2 receptor to compare their blocking efficacy with the control drug. The ligand-receptor complexes' accuracy in preventing the Spike (S) protein of SARS-CoV-2 penetration inside the host cells has been analyzed through hydrogen-hydrophobic bond interactions, principal component analysis (PCA), root mean square deviation (RMSD), root mean square fluctuation (RMSF), and B-Factor. Advanced in silico programming language and bioanalytical software were used for high throughput and authentic results. RESULTS: ADMET and QSAR revealed Rhamnetin, Lactupicrin, Rhinacanthin D, Flemiflavanone D, and Exiguaflavanone A as the ligands of our interest to be compared with the control Cassiarin D. According to the molecular docking binding affinity to block ACE2 receptor, the efficiency mountings were Rhinacanthin D > Flemiflavanone D > Lactupicrin > Exiguaflavanone A > Rhamnetin. The binding affinity of the Cassiarin D-ACE2 complex was (-10.2 KJ/mol) found inferior to the Rhinacanthin D-ACE2 complex (-10.8 KJ/mol), referring to Rhinacanthin D as a more stable candidate to use as drugs. The RMSD values of protein-ligand complexes evaluated according to their structural conformation and stable binding pose ranged between 0.1~2.1 Å. The B-factor showed that very few loops were present in the protein structure. The RMSF peak fluctuation regions ranged 5-250, predicting efficient ligand-receptor interactions. CONCLUSION: The experiment sequentially measures all the parameters required in referring to any pharmacophore as a drug, considering which all aromatic components analyzed in the study can strongly be predicted as target-specific medication against the novel coronavirus 2019 infection.

In ovo inoculation of duck embryos with different strains of Bacillus cereus to analyse their synergistic post-hatch anti-allergic potentialities.

BACKGROUND: Bacillus cereus is a Gram-positive, facultative anaerobic bacteria with few strains reported to be used as probiotics for animals and birds in recent times if the doses are formulated properly. OBJECTIVES: To analyse the synergistic anti-allergic potentiality of different Bacillus cereus strains on experimental in ovo and in vitro duck model, as probiotic immune stimulant. MATERIALS AND METHODS: Different strains of Bacillus cereus from 29 isolates were identified through 16S rRNA gene sequencing from the milk samples of buffalo breeds of South Asia. The probiotic properties were tested in aspects of gram staining, catalase test, coagulase, test, bile salt tolerance, pH tolerance and phenol tolerance test. MIC50 and MIC90 levels were profiled using nine different antibiotics, and antimicrobial activity against eight different enteric pathogens was assessed. Finally, the test strains of Bacillus cereus (Colony Forming Unit [CFU] 30X1011 ) were combined-infused at different concentrations in embryonated duck eggs to assess the post-hatch anti-allergic effects against histamine-induced allergic reaction and their immunoglobulin E (IgE) level was tested. RESULTS: Molecular identification confirmed the test strains as B. cereus HKS 1-1, B. cereus LOCK 1,002 and B. cereus BF2, which were all motile, spore-forming, catalase-positive and rod-shaped. All were 0.3% bile salt, 0.4% phenol and pH tolerant. Two-way ANOVA test P values revealed that B. cereus BF2 was statistically significant (p < .0014) in bile salt tolerance test. B. cereus HKS 1-1 was significant in phenol and pH tolerance at p < .0002 and p < .0489, respectively. Besides, the test strains showed antibiotic sensitivity and antimicrobial activity to different enteric pathogens. In vivo model referred the test strains as effective in partial allergy reduction at same CFU but at different concentrations with p < .0001 among the groups. CONCLUSION: The isolated and characterized strains of B. cereus showed partial immune-stimulating potentiality against experimentally induced allergic reaction.

Antidiarrheal Efficacy of Probiotic Bacteria in Castor Oil Induced Diarrheal Mice.

Probiotics may offer a safe intervention for diarrheal diseases. The aim of the present study was the assessment of the antidiarrheal property of probiotic bacteria. For their antidiarrheal efficacy assessment, yogurt was prepared using the isolated bacteria from selective regional yogurt of Bangladesh, and mice model trails were conducted using castor oil induced diarrheal mice. The probiotic treatment was applied on three mice groups, each having 6 mice and their respective doses were 50 mL/kg body weight in treatment group (TG) 1, 100 mL/kg body weight in TG2, and 150 mL/kg body weight in TG3. A four week treatment of probiotic significantly (P<0.001) reduced the percentage (67.37%) of diarrhea in TG3 (150 mL yogurt/kg body weight). All the treatment groups showed a significant (P<0.001) increase in the latent periods, reduced the total fecal output, and frequency and fecal water content compared to the negative control group. Serum electrolytes (Na+ and K+) and total protein levels were higher in the TG3 compared to the negative control group. Further research regarding molecular characterization and identification of specific genes and proteins of interest may help to develop the next generation bacteriocins and antidiarrheal drugs.