Broad Efficacy Research Articles

MiR-191-5p suppresses PRRSV replication by targeting porcine EGFR to enhance interferon signaling.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR's antiviral response. Furthermore, miR-191-5p's broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.

Centaurea dimorpha Viv. (Asteraceae) growing in Algeria extracts as a promising natural cosmetic active ingredient: Broad-spectrum photoprotection and antioxidant efficacy

Recently, plants have been considered as a valuable natural source of cosmetic active ingredientsowing to their sustainability and weak toxicity. Thus, this study was conducted to investigate the cosmetic efficacy of Centaurea dimorpha Viv (Asteraceae), an endemic species of North Africa, as a promising natural cosmetic active ingredient. In the present study, Ethyl acetate and Butanolic extracts obtained from powdered Centaurea dimorpha aerial parts were investigated for their phenolic and flavonoid contents, which were evaluatedvia Folin-ciocalteu reagent and aluminium chloride methods, the in vitro antioxidant potential was evaluated by DPPH radical scavenging,phosphomolybdenum and phenanthroline assays, the UVB and broad spectrum protective efficacy was spectrophotometrically assessed by measuring SPF, UVA/UVB ratio and critical wavelength (CW) indices. The highest levels of TPC and TFCwere recorded by the ethyl-acetate extract (119.20 ± 0.32 µg GAE mg-1, 50.65 ± 0.43 µg QEmg-1, respectively). Similarly, this extract displayed a significant antioxidant effect, particularly in the phenanthroline assay (152.63 ± 0.49 µg AAEmg-1). Ethyl acetate extract also showed UVB and broad-spectrum (UVB-UVA) protective efficacy (SPF=12.30 ± 0.001, UVA/UVB ratio=0.63 ± 0.001, λc= 371). The results obtained show the possibility to use Ethyl acetate extract as a promising active ingredient for sunscreen formulations.

Investigation of acetyl-CoA carboxylase-inhibiting herbicides that exhibit soybean crop selectivity.

The sustainable control of weed populations, particularly resistant species, is a significant challenge in agriculture around the world. The α-aryl-keto-enol (aryl-KTE) class of acetyl-CoA carboxylase (ACCase)-inhibiting herbicides represent a possible solution for the control of resistant grasses even though achieving crop selectivity remains a challenge. Herein, we present some of our investigations into identifying the most promising structural features within the aryl-KTE class that give the highest chance of achieving soybean crop selectivity, whilst also maintaining strong and broad efficacy against problematic weed species. We further examined our results by preparing new aryl-KTE molecules which were evaluated in glasshouse screening assays for their herbicidal efficacy as well as their soybean selectivity. We consider that uniting this approach with other optimization criteria, such as toxicological and environmental safety profiles, will enable the streamlining of crop protection optimizations programmes, ultimately delivering safer and more sustainable solutions to farmers and consumers. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma.

ADT-1004 displayed robust antitumor activity in aggressive and clinically relevant PDAC models with unique tumor specificity to block RAS activation and MAPK signaling in RAS mutant cells. As a pan-RAS inhibitor, ADT-1004 has broad activity and potential efficacy advantages over allele-specific KRAS inhibitors by averting resistance. These findings support clinical trials of ADT-1004 for KRAS mutant PDAC.

Adaptive multi-epitope targeting and avidity-enhanced nanobody platform for ultrapotent, durable antiviral therapy.

Pathogens constantly evolve and can develop mutations that evade host immunity and treatment. Addressing these escape mechanisms requires targeting evolutionarily conserved vulnerabilities, as mutations in these regions often impose fitness costs. We introduce adaptive multi-epitope targeting with enhanced avidity (AMETA), a modular and multivalent nanobody platform that conjugates potent bispecific nanobodies to a human immunoglobulin M (IgM) scaffold. AMETA can display 20+ nanobodies, enabling superior avidity binding to multiple conserved and neutralizing epitopes. By leveraging multi-epitope SARS-CoV-2 nanobodies and structure-guided design, AMETA constructs exponentially enhance antiviral potency, surpassing monomeric nanobodies by over a million-fold. These constructs demonstrate ultrapotent, broad, and durable efficacy against pathogenic sarbecoviruses, including Omicron sublineages, with robust preclinical results. Structural analysis through cryoelectron microscopy and modeling has uncovered multiple antiviral mechanisms within a single construct. At picomolar to nanomolar concentrations, AMETA efficiently induces inter-spike and inter-virus cross-linking, promoting spike post-fusion and striking viral disarmament. AMETA's modularity enables rapid, cost-effective production and adaptation to evolving pathogens.

Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid.

Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with the AMF receptor, regulating cancer cell motility, proliferation, metastasis, and angiogenesis through autocrine and paracrine pathways. However, studies verifying the synergistic effect of the combined use of anti-cancer drugs extracted from plants and AMF treatment are insufficient. The effects of AMF-derived peptide sequences were evaluated in HT29 and SW620 colorectal cancer (CRC) cell lines. The study assessed the impact of AMF peptides on cell proliferation, colony formation, the Nicotinamide Adenine Dinucleotide Phosphate/Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADP+/NADPH) ratio, and reactive oxygen species (ROS) generation in these CRC cells. Additionally, the combined effect of AMF peptides and glycyrrhetinic acid (GA), a compound derived from licorice plants, was investigated by analyzing cell proliferation, colony formation, ROS production, and cell cycle progression in CRC cells. AMF peptides significantly inhibited CRC cell growth (p < 0.05), decreased colony formation (p < 0.05), and increased the NADP+/NADPH ratio (p < 0.05) and ROS production (p < 0.001). When combined with GA, AMF peptides enhanced GA's effects on CRC cells, further suppressing cell growth (p < 0.05) and colony formation (p < 0.05) while increasing ROS generation (p < 0.05). The synergy between AMF peptides and GA, derived from licorice plants, suggests the potential for combined peptide-phytochemical therapy for treating CRC.

Causal relationship between novel antidiabetic drugs and ischemic stroke: a drug-targeted Mendelian randomization study.

The escalating global economic burden of ischemic stroke poses a significant public health challenge amid global aging trends. The broad therapeutic efficacy of new antidiabetic drugs may offer new options in the prevention and treatment of ischemic stroke. Consistent conclusions regarding the relationship between novel antidiabetic agents and the risk of ischemic stroke remain elusive, and the causal relationship deserves further investigation. Three novel antidiabetic drug targets were selected, and cis-expression quantitative trait loci (cis-eQTL) were screened as instrumental variables. Genetic association data for ischemic stroke were obtained from the Genome-wide Association Study (GWAS) database. Mendelian randomization (MR) analysis, facilitated by R software, calculated MR estimates for each single nucleotide polymorphism (SNP), and meta-analysis was performed using five methods. To ensure robustness, sensitivity analyses, heterogeneity analyses, horizontal pleiotropy analyses, and co-localization analyses were conducted for significant MR associations. Three eQTLs for antidiabetic drug genes served as instrumental variables, utilizing a GWAS dataset comprising 34,217 cases and 406,111 controls for ischemic stroke. Genetic variants in glucagon-like peptide-1 receptor agonists (GLP-1 RA) targets exhibited a positive correlation with ischemic stroke risk (OR 1.06, 95% CI 1.04-1.08, P = 0.000), while genetic variation in dipeptidyl peptidase 4 inhibitors (DPP-4i) targets showed a negative association with ischemic stroke risk (OR 0.93, 95% CI 0.89-0.97, P = 0.003). Sensitivity analyses supported robust conclusions, revealing no heterogeneity or horizontal pleiotropy. This study found that GLP-1 RA and DPP-4i were associated with an increased risk of ischemic stroke by MR analysis. Although sensitivity analyses provide support for this result, it contradicts previous knowledge. Therefore, the results of this study still need to treated with caution. Updated and more in-depth GWAS data and high-quality real-world data are expected to validate the results.

Comparison between clinical and cytological findings in chronic rhinosinusitis with nasal polyps treated with Dupilumab.

Biologics represent a new therapeutic strategy for severe and recurrent chronic rhinosinusitis with nasal polyps (CRSwNP). Usually, their actual therapeutic effectiveness is assessed by reduction in nasal polyps and/or improvement in nasal symptoms and quality of life. However, these measures do not consider nasal immunophlogosis, which can be evaluated through nasal cytology. The purpose of this study was to assess not only the clinical impact but also the cellular changes in the nasal inflammatory infiltrate observed through nasal cytology of CRSwNP patients treated with Dupilumab for 24 months. Fifty-five CRSwNP patients treated with Dupilumab were collected. Patients were evaluated before starting treatment and at one, three, six, nine months, one year, one and a half years, and two years after the first drug administration. During follow-up visits patients underwent endoscopic evaluation, nasal symptoms and quality of life assessment, complete blood count and nasal cytology. During follow-up, significant improvement was found in Nasal Polyps Score (NPS), nasal patency, olfaction, Sino-Nasal Outcome Test (SNOT-22) score, and Visual Analogue Scale (VAS). Regarding nasal cytology, a reduction in eosinophils and mast cells in the cellular infiltrate was observed over the two-year follow-up period compared to baseline. Dupilumab has demonstrated broad efficacy in the management of CRSwNP from both clinical and cytological findings. Further studies are needed to confirm our findings and evaluate the biologics' impact on nasal mucosal inflammatory cells by nasal cytology with the aim of better identifying each patient's endotype and predicting the response to biologics.

MHCI trafficking signal‐based mRNA vaccines strengthening immune protection against RNA viruses

AbstractThe major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

Calcipotriol/Betamethasone Dipropionate for the Treatment of Psoriasis: Mechanism of Action and Evidence of Efficacy and Safety versus Topical Corticosteroids.

The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management.

White light-driven enhanced cerium-doped carbon dots activity to combat multidrug-resistant bacterial infection

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

Systematic review on the safety of the use of quinolones in the pediatric population

Background: The safety of fluoroquinolones in the pediatric population has been a matter of concern due to the potential for adverse effects such as growth cartilage toxicity. Despite their broad antimicrobial spectrum and efficacy, the prescription of fluoroquinolones in children and adolescents is limited by the risk of arthralgias and other side effects. This study aims to evaluate the safety of fluoroquinolones in pediatric patients and the impact of regulatory actions on their prescription. Material and methods: A systematic review of studies investigating the safety of fluoroquinolones in the pediatric population was conducted. Studies that met specific inclusion criteria were selected, and relevant information on the decrease in fluoroquinolone prescriptions and their adverse effects was extracted. Results: In the study on the safety and tolerability of quinolones in the pediatric population, 22% (199/904) of patients experienced adverse events following treatment with quinolones. Gastrointestinal disorders, such as nausea and diarrhea, were the most frequent, affecting 12% (108/904) of patients. This was followed by skin rashes and effects on the central nervous system, at 5% (45/904) and 3% (27/904) respectively. Moxifloxacin demonstrated good tolerability across all age cohorts, without significant joint or neuropathic adverse findings. Specific safety studies of moxifloxacin confirmed its safety, showing no significant differences in safety variables compared to other antibiotics. Conclusion: It is crucial to continue monitoring the safety of fluoroquinolones in the pediatric population to ensure an adequate balance between the benefits and risks of their use.

Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics.

The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge.

Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.

The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates. Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay's Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism. WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates. Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.

Comparison of the intrageneric neutralization scope of monospecific, bispecific/monogeneric and polyspecific/monogeneric antisera raised in horses immunized with sub-Saharan African snake venoms.

Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.

AN OVERVIEW OF SOME HERBAL ANTIDEPRESSANT PLANTS

There are numerous ways to categorize and treat depression, which is a diverse mood disease. The illness is caused by factors such as 5-HT, NA, and MAO-A inhibition and stimulation. Reduced curiosity about pleasure, feelings of inappropriate guilt or worthlessness, a drop in hunger and sexual desire, sleeplessness, and persistent suicidal thoughts are some of the symptoms. There are several synthetic medications used to treat depression, but not all of them make patients happy, and some of them may have negative side effects. Many have turned to well-liked traditional herbal remedies to avoid the negative effects of allopathic therapy. Due to their broad application, therapeutic efficacy, and little to negligible adverse effects, herbal medications are currently used worldwide. Several medicinal plants and medicines derived from these plants have shown antidepressant properties by the combined effect of their medicinal constituents. We discuss promising novel medicinal products targets for the management of major depressive illness in this review. We address the potential antidepressant benefits of selectively targeting receptors, including opioid, G-protein-coupled, and metabotropic glutamate receptors. Since they may also have therapeutic value, we also talk about substances that target biological processes, including inflammation, the gut microbiota, the cholesterol biosynthesis pathway, and the hypothalamic-pituitary-adrenal axis. Lastly, we offer a synopsis of all the plants displayed in graphical format, together with an overview of the antidepressant plants which currently are widely accessible.

BacScan: a novel genome-wide strategy for uncovering broadly immunogenic proteins in bacteria.

In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan's adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.

Virus-like particle-based multipathogen vaccine of FMD and SVA elicits balanced and broad protective efficacy in mice and pigs

Inactivated vaccines lack the capability to serologically differentiate between infected and vaccinated animals, thereby impeding the effective eradication of pathogen. Conversely, vaccines based on virus-like particles (VLPs) emulate natural viruses in both size and antigenic structure, presenting a promising alternative to overcome these limitations. As the complexity of swine infectious diseases increases, the increase of vaccine types and doses may intensify the stress response. This exacerbation can lead to diminished productivity, failure of immunization, and elevated costs. Given the critical dynamics of co-infection and the clinically indistinguishable symptoms associated with foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), there is a dire need for an efficacious intervention. To address these challenges, we developed a combined vaccine composed of three distinct VLPs, specifically designed to target SVA and FMDV serotypes O and A. Our research demonstrates that this trivalent VLP vaccine induces antigen-specific and robust serum antibody responses, comparable to those produced by the respective monovalent vaccines. Moreover, the immune sera from the combined VLP vaccine strongly neutralized FMDV type A and O, and SVA, with neutralization titers comparable to those of the individual vaccines, indicating a high level of immunogenic compatibility among the three VLP components. Importantly, the combined VLPs vaccines-immunized sera conferred efficient protection against single or mixed infections with FMDV type A and O, and SVA viruses in pigs. In contrast, individual vaccines could only protect pigs against homologous virus infections and not against heterologous challenges. This study presents a novel combined vaccines candidate against FMD and SVA, and provides new insights for the development of combination vaccines for other viral swine diseases.

Facile Synthesis of Cu-Doped TiO2 Particles for Accelerated Visible Light-Driven Antiviral and Antibacterial Inactivation.

In this work, we present a facile and scalable hydrolysis-based route for the synthesis of copper-doped TiO2 particles for highly effective light-activated antiviral and antibacterial applications. The performance of the synthesized Cu-doped TiO2 particles is then evaluated using solution-phase antimicrobial photodynamic inactivation assays. We demonstrate that the Cu-doped TiO2 particles can successfully inactivate a wide range of pathogens with exposure to light for 90 min, including bacteria ranging from methicillin-resistant Staphylococcus aureus (99.9999%, ∼6 log units) to Klebsiella pneumoniae (99.93%, ∼3.3 log units), and viruses including feline calicivirus (99.94%, ∼3.4 log units) and HCoV-229E (99.996%, ∼4.6 log units), with the particles demonstrating excellent robustness toward photobleaching. Furthermore, a spray-coated polymer film, loaded with the synthesized Cu-doped TiO2 particles achieves inactivation of methicillin-resistant S. aureus up to 99.998% (∼4.8 log units). The presented results provide a clear advance forward in the use of metal-doped TiO2 for aPDI applications, including the scalable synthesis (kg/day) of well-characterized and robust particles, their facile incorporation into a nontoxic, photostable coating that may be easily and cheaply applied to a multitude of surfaces, and a broad efficacy against drug-resistant Gram-positive and Gram-negative bacteria, as well as against enveloped and nonenveloped viruses.

Development of protease resistant and non-cytotoxic Jelleine analogs with enhanced broad spectrum antimicrobial efficacy

Short systemic half- life of Antimicrobial Peptides (AMP) is one of the major bottlenecks that limits their successful commercialization as therapeutics. In this work, we have designed analogs of the natural AMP Jelleine, obtained from royal jelly of apis mellifera. Among the designed peptides, J3 and J4 were the most potent with broad spectrum activities against a varied class of ESKAPE pathogens and fungus C. albicans. All the developed peptides were more effective against Gram-negative bacteria in comparison to the Gram-positive pathogens, and were especially effective against P. aeruginosa and C. albicans.J3 and J4 were completely trypsin resistant and serum stable, while retaining the non-cytotoxicity of the parent Jelleine, Jc. The designed peptides were membranolytic in their mode of action. CD and MD simulations in the presence of bilayers, established that J3 and J4 were non-structured even upon membrane binding and suggested that biological properties of the AMPs were innocent of any specific secondary structural requirements. Enhancement of charge to increase the antimicrobial potency, controlling the hydrophobic-hydrophilic balance to maintain non-cytotoxicity and induction of unnatural amino acid residues to impart protease resistance, remains some of the fundamental principles in the design of more effective antimicrobial therapeutics of the future, which may help combat the quickly rising menace of antimicrobial resistance in the microbes.