Narrow Spectrum Of Activity Research Articles

Dual Inhibition of Parasitic Targets: A Valuable Strategy to Treat Malaria and Neglected Tropical Diseases.

Despite the countless efforts made in the last decades, malaria and neglected tropical diseases remain a high-impact health problem in developing countries. Malaria is one of the most severe parasitic diseases, with over 200 million cases and 400,000 deaths in 2019. Parasitic diseases caused by trypanosomatidae, namely Human African Trypanosomiasis, Chagas disease, and leishmaniasis, register the highest rates of mortality amongst all the neglected tropical diseases. In this scenario, chemotherapy remains the first strategy, which aims to control and eliminate these diseases. However, the use of outdated, unsafe, and poorly effective drugs, together with the onset of resistance, prompted the researchers to identify new and valid targets. The innovative idea, aimed at the development of multi-target ligands addressing two different targets playing key roles in parasite survival, could represent a valuable strategy. Thanks to this approach, the wellknown limitations characterizing the antiparasitic drugs, such as toxicity, rapid resistance onset and narrow spectrum of action, could be overcome. In this review, we now describe the most recent multi-target ligands endowed with antiparasitic effects reported in the literature, focusing our attention on their binding with the targets, inhibitory activities, and potential therapeutic applications.

Vibrio spp. and Their Vibriocin as a Vibriosis Control Measure in Aquaculture.

Vibriosis disease is a major threat to the aquaculture industry caused by Vibrio spp. that are often resistant to antibiotics. Alternative controlling measures such as bacteriocins could be effective due to their narrow-spectrum activity. Hence, this systematic literature review (SLR) was carried out to review the feasibility of Vibrio spp. and their vibriocins to be used as a vibriosis control measure in aquaculture. A literature search using the web of science (WOS) and SCOPUS databases resulted in 42 unique articles which were reviewed. The results showed that Vibrio spp. could be used as a probiotic to control vibriosis, but not recommended due to their opportunistic nature and pathogenesis. Vibriocin showed narrow-spectrum activity against Vibrio spp. including highly pathogenic strains such as V. alginolyticus, V. harveyi, and V. parahaemolyticus. This supported this review's hypothesis of using vibriocin as a targeted vibriosis control measure. Vibrio cholerae was the most studied and showed the highest inhibition range, inhibiting 13 different vibrio and non-vibrio species. Various innovations were reported in the field and vibriocins can now be produced on large scales using whole-cell culture. Vibriocins were structurally diverse, large molecular weight, and relatively heat stable. These vibriocins mainly inhibited the cell wall but could have other novel mechanisms. These properties could affect the extraction process as well as applications in aquaculture, hence, should be considered in future research.

ANTHELMINTIC FOR MIXED PARASITOSIS

The antiparasitic program, which provides specific treatment and prevention regimens for fascioliasis, dictyoculosis, strongylatosis of the gastrointestinal tract and other parasitoses is the most effective link aimed primarily at removing helminths and preventing infection. Taking into account the total economic damage when helminthofauna in animals is represented simultaneously by parasitic species, it is necessary to be armed with anthelmintics of a wide spectrum of action. With their help, it is possible to carry out preventive measures most effectively and forced deworming, taking into account the epizootic situation and the present background of pathogens of invasions in the farm. As a result of the research, the higher efficiency and prospects of using Santel in the long-term forecast and Santomectin compared with the basic drugs of a narrow spectrum of action. Santomectin, acting on the larval and adult stages of fascioles, prevents the development of acute fascioliasis, as well as its transition to a chronic form; prevents the release of eggs of fascioles into the external environment, chronically ill animals, all this has the best effect on the epizootic situation, especially before being driven to pasture, and ultimately on the health and productivity of animals; it allows solving the problem of mixed parasitosis that cause the greatest economic damage; anthelmintics that are not active for larval stages of fascioles, slightly prevent contamination of pastures with trematodes, for the destruction of which repeated treatments are necessary

Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile.

Fidaxomicin (Fdx) is widely used to treat Clostridioides difficile (Cdiff) infections, but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains unknown. Cdiff infections are a leading cause of nosocomial deaths1. Fidaxomicin, which inhibits RNA polymerase, targets Cdiff with minimal effects on gut commensals, reducing recurrence of Cdiff infection2,3. Here we present the cryo-electron microscopy structure of Cdiff RNA polymerase in complex with fidaxomicin and identify a crucial fidaxomicin-binding determinant of Cdiff RNA polymerase that is absent in most gut microbiota such as Proteobacteria and Bacteroidetes. By combining structural, biochemical, genetic and bioinformatic analyses, we establish that a single residue in Cdiff RNA polymerase is a sensitizing element for fidaxomicin narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen.

In vitro susceptibility of swine pathogens to feed additives and active ingredients with potential as antibiotic replacements.

The rise in antibiotic resistance requires the reduction of antibiotic use in all sectors. In animal production, many commercial alternatives to antibiotics have been developed for incorporation into feeds, but a lack of evidence on their antibacterial activity limits confidence in their application. We aim to compare the antibacterial activity of feed additives and active ingredients to better understand their usefulness. The antibacterial activity of 34 active ingredients and feed additives, including medium- and short-chain organic acids and essential oils, was tested against pure cultures of five bacterial swine pathogens. Antibacterial activity was observed using an agar plug diffusion method and quantified via broth microdilution. A diverse range of antibacterial activities were observed. The highest inhibitory activity against Staphylococcus aureus and Streptococcus suis was exhibited by the C12 monoglyceride (0.49mgml-1 ). The monoglyceride of C12 was more effective than C12:0 against Strep. suis, but neither C12:0 nor its monoglyceride showed efficacy against the gram-negative micro-organisms tested. The most active against Escherichia coli were the C6:0 medium-chain organic acids and potassium diformate (1.95mgml-1 ). For Salmonella Typhimurium, potassium diformate, sodium diformate, and a blend of C8:0/C10:0 (each 1.96mgml-1 ), and for Actinobacillus pleuropneumoniae, eugenol (0.49mgml-1 ) showed the most promising activity. We identified broad-spectrum antibacterial activity, such as the C6:0 MCOA, and those with interesting narrow-spectrum activity, notably the killing of Strep. suis by C12 monoglyceride. We have identified additives that show the most promising bioactivity against specific pathogens. We broadly compare a large collection of feed additives and active ingredients for their antibacterial activity against a diverse panel of bacterial swine pathogens. This provides a solid base of evidence which can drive the development of feed supplementation strategies with the aim of reducing dependency on antibiotic use in swine production.

Combined antimicrobial effect of bacteriocins with other hurdles of physicochemic and microbiome to prolong shelf life of food: A review

Bacteriocins are ribosomally synthesized peptides to inhibit food spoilage bacteria, which are widely used as a kind of food biopreservation. The role of bacteriocins in therapeutics and food industries has received increasing attention across a number of disciplines in recent years. Despite their advantages as alternative therapeutics over existing strategies, the application of bacteriocins suffers from shortcomings such as the high isolation and purification cost, narrow spectrum of activity, low stability and solubility and easy enzymatic degradation. Previous studies have studied the synergistic or additive effects of bacteriocins when used in combination with other hurdles including physics, chemicals, and microbes. These combined treatments reduce the adverse effects of chemical additives, extending the shelf life of food products while guaranteeing food quality. This review highlights the advantages and disadvantages of bacteriocins in food preservation. It then reviews the combined effect and mechanism of different hurdles and bacteriocins in enhancing food preservation in detail. The combination of bacterioncins and other hurdles provide potential approaches for maintaining food quality and food safety.

Ribonucleotide reductase, a novel drug target for gonorrhea.

Antibiotic-resistant Neisseria gonorrhoeae (Ng) are an emerging public health threat due to increasing numbers of multidrug resistant (MDR) organisms. We identified two novel orally active inhibitors, PTC-847 and PTC-672, that exhibit a narrow spectrum of activity against Ng including MDR isolates. By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). Resistance mutations in Ng map to the N-terminal cone domain of the α subunit, which we show here is involved in forming an inhibited α4β4 state in the presence of the β subunit and allosteric effector dATP. Enzyme assays confirm that PTC-847 and PTC-672 inhibit Ng RNR and reveal that allosteric effector dATP potentiates the inhibitory effect. Oral administration of PTC-672 reduces Ng infection in a mouse model and may have therapeutic potential for treatment of Ng that is resistant to current drugs.

Two-Metal Ion-Dependent Enzymes as Potential Antiviral Targets in Human Herpesviruses.

ABSTRACTThe majority of drug discovery efforts against herpesviruses have focused on nucleoside analogs that target viral DNA polymerases, agents that are associated with dose-limiting toxicity and/or a narrow spectrum of activity. We are pursuing a strategy based on targeting two-metal ion-dependent (TMID) viral enzymes. This family of enzymes consists of structurally related proteins that share common active sites containing conserved carboxylates predicted to coordinate divalent cations essential for catalysis. Compounds that target TMID enzymes, such as HIV integrase and influenza endoribonuclease, have been successfully developed for clinical use. HIV integrase inhibitors have been reported to inhibit replication of herpes simplex virus (HSV) and other herpesviruses; however, the molecular targets of their antiviral activities have not been identified. We employed a candidate-based approach utilizing several two-metal-directed chemotypes and the potential viral TMID enzymatic targets in an effort to correlate target-based activity with antiviral potency. The panel of compounds tested included integrase inhibitors, the anti-influenza agent baloxavir, three natural products previously shown to exhibit anti-HSV activity, and two 8-hydroxyquinolines (8-HQs), AK-157 and AK-166, from our in-house program. The integrase inhibitors exhibited weak overall anti-HSV-1 activity, while the 8-HQs were shown to inhibit both HSV-1 and cytomegalovirus (CMV). Target-based analysis demonstrated that none of the antiviral compounds acted by inhibiting ICP8, contradicting previous reports. On the other hand, baloxavir inhibited the proofreading exonuclease of HSV polymerase, while AK-157 and AK-166 inhibited the alkaline exonuclease UL12. In addition, AK-157 also inhibited the catalytic activity of the HSV polymerase, which provides an opportunity to potentially develop dual-targeting agents against herpesviruses.

Advances in Antifungal Drug Development: An Up-To-Date Mini Review.

The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry.

Ab initio Designed Antimicrobial Peptides Against Gram-Negative Bacteria

Antimicrobial peptides (AMPs) are ubiquitous amongst living organisms and are part of the innate immune system with the ability to kill pathogens directly or indirectly by modulating the immune system. AMPs have potential as a novel therapeutic against bacteria due to their quick-acting mechanism of action that prevents bacteria from developing resistance. Additionally, there is a dire need for therapeutics with activity specifically against Gram-negative bacterial infections that are intrinsically difficult to treat, with or without acquired drug resistance. Development of new antibiotics has slowed in recent years and novel therapeutics (like AMPs) with a focus against Gram-negative bacteria are needed. We designed eight novel AMPs, termed PHNX peptides, using ab initio computational design (database filtering technology combined with the novel positional analysis on APD3 dataset of AMPs with activity against Gram-negative bacteria) and assessed their theoretical function using published machine learning algorithms, and finally, validated their activity in our laboratory. These AMPs were tested to establish their minimum inhibitory concentration (MIC) and half-maximal effective concentration (EC50) under CLSI methodology against antibiotic resistant and antibiotic susceptible Escherichia coli and Staphylococcus aureus. Laboratory-based experimental results were compared to computationally predicted activities for each of the peptides to ascertain the accuracy of the computational tools used. PHNX-1 demonstrated antibacterial activity (under high and low-salt conditions) against antibiotic resistant and susceptible strains of Gram-positive and Gram-negative bacteria and PHNX-4 to -8 demonstrated low-salt antibacterial activity only. The AMPs were then evaluated for cytotoxicity using hemolysis against human red blood cells and demonstrated some hemolysis which needs to be further evaluated. In this study, we successfully developed a design methodology to create synthetic AMPs with a narrow spectrum of activity where the PHNX AMPs demonstrated higher antibacterial activity against Gram-negative bacteria compared to Gram-positive bacteria. Thus, these peptides present novel synthetic peptides with a potential for therapeutic use. Based on our findings, we propose upfront selection of the peptide dataset for analysis, an additional step of positional analysis to add to the ab initio database filtering technology (DFT) method, and we present laboratory data on the novel, synthetically designed AMPs to validate the results of the computational approach. We aim to conduct future in vivo studies which could establish these AMPs for clinical use.

Modern chemical disinfectants and antiseptics. Part I

Aim. To generalize and systematize information on the properties of modern chemical disinfectants and antiseptic agents (DA and AA).Results and discussion. The review provides generalized and systematized information on the properties of modern chemical DA and AA – alkylating reagents, aldehydes, amides, amidines, bisguanidines, dyes, halogenated reagents, halogens and their complexes, 2-nitrofuran derivatives. The classification of DA and AA by their chemical structure was carried out. The activity spectra, possible application ways and forms of DA and AA were given. Their toxicity and impact on the environment were described as well.Conclusions. On the basis of the analysis carried out it was shown that aldehydes, halogen-active compounds and halogen-containing complexes are modern effective DA and AA with a wide spectrum of biocidal action. Amides, amidines and bisguanidines are characterized by a narrow spectrum of activity. Dyes and 2-nitrofuran derivatives are old-fashioned antiseptics.

Influence of Gd doping on morphological, toxicity and magnetic properties of ZnO nanorods

Properties of chemically synthesized Zn1−xGdxO (x = 0.01, 0.03 and 0.05) nanorods were explored through microstructural, morphological, toxicity and magnetic characterizations. Hexagonal wurtzite structure of all the samples without any impurity phases was confirmed by X-ray diffraction characterization. The micrographs of transmission electron microscope and field emission scanning electron microscope revealed the rod shape morphology of the samples. A systematic evolution of room temperature ferromagnetism of ZnO nanorods with increasing Gd doping content was observed. Gd doped ZnO nanorods showed narrow-spectrum antibacterial activity against the most opportunistic Gram-positive pathogen bacterium, S. aureus as compared to commercial ZnO. From cytotoxicity assessment with Caenorhabditis elegans and Danio rerio, the samples were non-toxic or showed little toxicity at the highest concentration tested (100 µg/mL) except for 1% Gd doped ZnO. Our study demonstrates the possible usefulness of the materials in spintronic, magnetic media device as well as bio-medical applications.

Reinvestigation of the structure-activity relationships of isoniazid

Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of the pyridyl nitrogen atom, isomerization of the pyridine nitrogen to other positions, replacement of the pyridine ring with isosteric heterocycles, and modification of the hydrazide moiety of INH abolishes antitubercular activity. Similarly, substitution of the pyridine ring at the 3-position is not tolerated while substitution at the 2-position is permitted with 2-methyl-INH 9 displaying antimycobacterial activity comparable to INH. To assess the specific activity of this series of INH analogs against mycobacteria, we assayed them against a panel of gram-positive and gram-negative bacteria, as well as a few fungi. As expected INH and its analogs display a narrow spectrum of activity and are inactive against all non-mycobacterial strains evaluated, except for 4, which has modest inhibitory activity against Cryptococcus neoformans. Our findings provide an updated analysis of the structure-activity relationship of INH that we hope will serve as useful resource for the community.

POTENTIAL RISKS IN MODERN ANTIBIOTIC THERAPY

Knowledge of the safety profile of antibacterial drugs is important for rational pharmacotherapy with antibiotics. The purpose of this information is to help the doctor, pharmacist and patient to (quickly) "navigate" in the safety of antibiotics to implement one of the basic principles of pharmacotherapy "Do no harm!". The aim of the study. Analysis of possible potential risks in modern antibiotic therapy. Materials and methods. Analysis of data from the scientific literature on the side effects of antibiotics. Results. Most antibiotics have a wide spectrum of antimicrobial action, much less of them have a narrow spectrum of activity, but all of them have side effects (SE). In particular, the neurotoxicity of penicillins and fluoroquinolones is a consequence of their antagonism with GABA. The latter mechanism is also responsible for the neurotoxicity of carbapenens, monobactams and cephalosporins. Cardiotoxicity and hematotoxicity of benzylpenicillins are the result of inhibition of tissue respiration and the process of converting fibrinogen to fibrin, which causes bleeding. The hematotoxicity of carbopenicillins, monobactams and cephalosporins is associated with the inhibition of the conversion of vicasol (vit. K) into its active form, as well as the obstruction of its synthesis due to the suppression of normal intestinal microflora (the main producer of endogenous vit. K). The nephrotoxicity of aminoglycosides and vancomycin is associated with the accumulation of these drugs in the cells of the proximal renal tubules and impaired enzyme activity (Na+-, K+-, ATP; respiratory, etc.), which leads to interstitial nephritis. Ototoxicity of antibiotics is observed when they are used over the age of 60 – a factor that predisposes to ototoxicity. Conclusions. In order to conduct effective antibiotic therapy, it is very important to take into account the side effects that are characteristic of certain groups of antibiotics and each is representatively individual.

Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety.

Cutaneous rosacea is a common inflammatory skin disorder that often presents with facial papulopustular lesions that are frequently bothersome to patients. Studies have shown oral sarecycline to be effective and safe for acne, with a low risk of side effects that are historically associated with other tetracycline-class drugs such as doxycycline and minocycline, in addition to offering a reduced risk of emergence of resistant bacteria due to its narrow-spectrum of antibiotic activity. Oral sarecycline is FDA-approved for the treatment of acne (2018). A pilot study to evaluate the efficacy and safety of oral sarecycline in papulopustular rosacea. A 12-week, prospective, parallel-group, investigator-blinded, controlled pilot study was completed evaluating once-daily sarecycline, using weight-based oral dosing as recommended for acne vs control (multivitamin tablet), for the treatment of moderate-to-severe papulopustular rosacea in adult subjects (n=102), aged ≥18 years. The primary efficacy endpoint was Investigator’s Global score (IGA; clear or almost clear) and percent reduction in inflammatory lesion count at week 12. Safety and tolerability assessments were performed as well. A total of 102 subjects were randomized; 97 completed the study. At week 12, IGA improvement was significantly greater for oral sarecycline when compared to the control (P<0.0001). Furthermore, absolute and percent reductions in inflammatory lesion counts were significantly greater in the sarecycline group for all weeks (4, 8, and 12) when compared to the control (P<0.001). Significant improvement in facial burning, erythema, and pruritus was reported in the sarecycline group, when compared to the control (P<0.05). No serious AEs were reported. Sarecycline was effective, safe, and well-tolerated for treating papulopustular rosacea in adults with marked superiority in efficacy compared to subjects in the control group. With its narrow-spectrum activity, oral sarecycline may be a good option for the treatment of papulopustular rosacea. Additional studies are warranted to confirm the positive results of this pilot study.

Resources Assessment for Penicillin Allergy Testing Performed by Pharmacists at the Patient's Bedside.

Background:False penicillin allergies lead to increased antimicrobial resistance, adverse effects, and health care costs by promoting the use of broad-spectrum antibiotics. The Infectious Diseases Society of America recommends the implementation of allergy testing.Objectives:The primary objective of this research was to estimate the number of pharmacist full-time equivalents (FTEs) required for an intervention aimed at determining penicillin allergy in hospitalized patients. Acceptance of pharmacists’ suggestions on antibiotic therapy are described.Methods:A quasi-experimental study was conducted in a 712-bed university hospital involving hospitalized patients with a suspected penicillin allergy and an infection treatable with penicillin. The time required for the intervention, which included a questionnaire, penicillin allergy testing (skin-prick test, intradermal injection, and oral provocation test), and recommendations on antibiotic therapy were measured to calculate the number of pharmacist FTEs.Results:A total of 55 patients were included. Scarification allergy testing was performed on 37, intradermal allergy test on 33, and oral provocation test on 26 patients. The intervention ruled out penicillin allergy in 26 patients, with no serious adverse effects. The intervention was associated with a median weekly pharmacist FTE of 0.15 (interquartile range = 0.12-0.25). The acceptance of pharmacists’ suggestions was high and led to 9 patients being switched to an antibiotic with a narrower spectrum of activity.Conclusions and Relevance:This study describes penicillin allergy testing and the number of median weekly hospital pharmacist FTEs required, which was approximately 0.15. These data may aid in the implementation of this safe intervention that promotes narrower-spectrum antibiotherapy.

The Role of Sialylation in Respiratory Viral Infection and Treatment.

Respiratory infections caused by viruses such as influenza and coronavirus are a serious global problem due to their high infection rates and potential to spark pandemics, such as the current COVID-19 pandemic. Although preventing these infections by using vaccines has been the most successful strategy to date, effective vaccines are not always available. Therefore, developing broad-spectrum anti-viral drugs to treat such infections is essential, especially in the case of immunocompromised patients or for outbreaks of novel virus strains. Sialic acids have been highlighted as a key molecule in the viral infection cycle, with terminally sialylated glycans acting as a target for several viral proteins involved in infection, particularly respiratory infection. Inhibitors of one such protein, neuraminidase, are the only anti-influenza drugs currently on the market. Problems with neuraminidase inhibitors, including the development of resistance and a relatively narrow spectrum of activity, drive the need for an improved understanding of the viral infection cycle and the development of more resilient, broader-spectrum anti-viral treatments. Hence, this review outlines the various roles played by sialic acids in respiratory viral infection and provides examples of drugs that exploit sialic acids to inhibit viral infections. It has been concluded that drugs targeting host cell expression of sialic acid could be especially well suited to inhibiting a broad spectrum of respiratory infections. This warrants the continued design and improvement of such drugs in an attempt to lessen the burden of respiratory infections.

Structural, optical, antimicrobial and ferromagnetic properties of Zn1−xLaxO nanorods synthesized by chemical route

Nanoparticles of Zn1−xLaxO (x = 0, 0.01, 0.03 and 0.05) were successfully synthesized by a cost-effective chemical method. The influences of La on the microstructural, optical, antimicrobial and magnetic properties of these ZnO nanoparticles were investigated. XRD studies revealed the presence of hexagonal wurtzite phase of ZnO without any impurity. The samples possess nanorod morphology as confirmed by FESEM and TEM analysis. The band gap of ZnO nanorods increased from 3.25 to 3.27 eV with increasing La concentration from 0% to 5%. The presence of various defects in our samples were identified by PL spectroscopy. Magnetic studies exposed the signature of ferromagnetism in all the samples at 300 K. The magnetization of ZnO nanorods is significantly enhanced by La doping. A maximum values of magnetization was observed for 1% La doped ZnO sample which is ~6 times more than for a pure ZnO nanorods. The contributions of oxygen vacancies towards the observed ferromagnetism were confirmed. The origin of ferromagnetism was enlightened on the basis of results of a BMP model. In vitro bioassays showed that synthesized nanorods exhibited narrow-spectrum antibacterial activity against Staphylococcus aureus that compared well with commercial ZnO, nanoparticles (Sigma). Furthermore, the synthesized nanorods when tested for toxicity against Caenorhabditis elegans, but show only low toxicity at 100 µg/mL. Toxicity in zebrafish was also limited. Based on their multifunctional properties, we believe that the synthesized ZnO nanorods could be beneficial for optical device applications in the UV range, spintronic devices, as well as for biomedical purposes.

Potential Novel Food-Related and Biomedical Applications of Nanomaterials Combined with Bacteriocins.

Bacteriocins are antimicrobial peptides or proteinaceous materials produced by bacteria against pathogens. These molecules have high efficiency and specificity and are equipped with many properties useful in food-related applications, such as food preservatives and additives, as well as biomedical applications, such as serving as alternatives to current antibacterial, antiviral, anticancer, and antibiofilm agents. Despite their advantages as alternative therapeutics over existing strategies, several limitations of bacteriocins, such as the high cost of isolation and purification, narrow spectrum of activity, low stability and solubility, and easy enzymatic degradation, need to be improved. Nanomaterials are promising agents in many biological applications. They are widely used in the conjugation or decoration of bacteriocins to augment the activity of bacteriocins or reduce problems related to their use in biomedical applications. Therefore, bacteriocins combined with nanomaterials have emerged as promising molecules that can be used in various biomedical applications. This review highlights the features of bacteriocins and their limitations in biomedical applications and provides a detailed overview of the uses of different nanomaterials in improving the limitations. Our review focuses on the potential applications of nanomaterials combined with bacteriocins as new designer molecules for use in future therapeutic strategies.

The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification.

We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.