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Keywords = in vitro infectious assays

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25 pages, 2588 KiB  
Article
Phytochemical Analysis and Therapeutic Potential of Tuberaria lignosa (Sweet) Samp. Aqueous Extract in Skin Injuries
by Manuel González-Vázquez, Ana Quílez Guerrero, Mónica Zuzarte, Lígia Salgueiro, Jorge Alves-Silva, María Luisa González-Rodríguez and Rocío De la Puerta
Plants 2025, 14(15), 2299; https://doi.org/10.3390/plants14152299 - 25 Jul 2025
Viewed by 337
Abstract
Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in [...] Read more.
Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article
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9 pages, 413 KiB  
Review
Co-Cultivation Assays for Detecting Infectious Human-Tropic Porcine Endogenous Retroviruses (PERVs)
by Joachim Denner
Int. J. Mol. Sci. 2025, 26(15), 7111; https://doi.org/10.3390/ijms26157111 - 23 Jul 2025
Viewed by 252
Abstract
Porcine endogenous retroviruses (PERVs) are integrated into the genome of all pigs. As they can be released as infectious virus particles capable of infecting human cells in vitro, they pose a potential risk for xenotransplantation involving pig cells or organs. To assess whether [...] Read more.
Porcine endogenous retroviruses (PERVs) are integrated into the genome of all pigs. As they can be released as infectious virus particles capable of infecting human cells in vitro, they pose a potential risk for xenotransplantation involving pig cells or organs. To assess whether pigs produce infectious human-tropic viruses, infection assays with human cells are required. There are three main types of assays. First is the incubation of human target cells with gamma-irradiated pig cells. This method ensures that viral transmission is assessed in the absence of replicating pig cells. However, gamma irradiation may alter gene expression in pig cells, potentially affecting the results. Second is the co-culture in a double-chamber system in which pig and human cells are separated by a porous membrane, preventing direct cell-to-cell contact. While this method allows for the detection of infection by free virus particles, it does not account for infection via cell-to-cell transmission, which is a common mode of retroviral infection. And third is the co-culture of pig cells with human cells expressing a resistance gene. The resistance gene allows selective elimination of pig cells upon the addition of a selection medium. This assay enables both free virus and cell-to-cell transmission as well as complete removal of pig cells, which may not be fully achieved in the first type of assay. The third assay best simulates the conditions of in vivo xenotransplantation. However, in all cases the selection of donor and recipient cells is crucial to the experimental outcome. Results only indicate whether a specific pig cell type releases PERVs and whether a specific human cell type is susceptible to infection. A negative infection result does not necessarily reflect the in vivo situation, in which a transplanted organ consists of multiple pig cell types interacting with a diverse range of human cells within a living organism. Knowledge of these limitations is important for authorities regulating clinical applications for xenotransplantation. Full article
(This article belongs to the Special Issue Microbial Infections and Novel Biological Molecules for Treatment)
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12 pages, 1648 KiB  
Article
The Isolation and Construction of an Infectious Clone for a Duck Adenovirus Type 3 Strain
by Haipeng Lu, Mei Tang, Zhifei Zhang, Mi Wu, Chunxiu Yuan, Xue Pan, Qinfang Liu, Qiaoyang Teng, Bangfeng Xu, Minghao Yan, Dawei Yan, Fenglong Wang and Zejun Li
Microorganisms 2025, 13(6), 1319; https://doi.org/10.3390/microorganisms13061319 - 5 Jun 2025
Viewed by 534
Abstract
A duck adenovirus type 3 strain, SD2019, was isolated from sick Muscovy ducks in our laboratory in 2019. To study the biological properties of the virus, an infectious clone of the SD2019 strain was successfully established. The plasmid containing the whole genome of [...] Read more.
A duck adenovirus type 3 strain, SD2019, was isolated from sick Muscovy ducks in our laboratory in 2019. To study the biological properties of the virus, an infectious clone of the SD2019 strain was successfully established. The plasmid containing the whole genome of DAdV-3 was digested with Pac I and the linearized DNAs were electortransfected into LMH cells; the cells showed cytopathic effects (CPEs) at 96 h post transfection and the rescued virus (rSD2019) was identified by PCR and indirect immunofluorescence assays (IFAs). The biological characteristics of strain rSD2019 were studied in vitro and in vivo and the results show that rSD2019 grew to similar titers as compared with the wild-type SD2019 strain in LMH cells, as well as showing similar replication and virulence in Muscovy ducks. The establishment of a reliable reverse genetics system for DAdV-3 provides a foundation for future studies of DAdV-3. Full article
(This article belongs to the Section Virology)
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18 pages, 3675 KiB  
Article
Virtual Screening of Novel Benzothiozinone Derivatives to Predict Potential Inhibitors of Mycobacterium Tuberculosis Kinases 2D-QSAR, Molecular Docking, MM-PBSA Dynamics Simulations, and ADMET Properties
by Abdelmadjid Guendouzi, Lotfi Belkhiri, Zakaria Slimani, Abdelkrim Guendouzi and Gautier Moroy
Int. J. Mol. Sci. 2025, 26(11), 5129; https://doi.org/10.3390/ijms26115129 - 27 May 2025
Viewed by 559
Abstract
Mycobacterium tuberculosis, the infectious agent behind tuberculosis (TB), underscores the significance of targeting enzymes such as arabinosyltransferases in drug development efforts. Benzothiozinone derivatives, which have been assessed for their effectiveness against TB, present a promising avenue for treatment. Utilizing a high virtual screening [...] Read more.
Mycobacterium tuberculosis, the infectious agent behind tuberculosis (TB), underscores the significance of targeting enzymes such as arabinosyltransferases in drug development efforts. Benzothiozinone derivatives, which have been assessed for their effectiveness against TB, present a promising avenue for treatment. Utilizing a high virtual screening quantitative structure–activity relationship (QSAR-VS), a set of forty Benzothiozinone (C1–C40) compounds were investigated to build a robust model with satisfactory performance metrics (R2 = 0.82, R2adj = 0.78, Ntest = 10, R2test = 0.70). This model enabled the creation of databases containing new derivatives for screening drug-like properties and predicting MIC activity in TB treatment. The best-scoring compounds were screened by molecular docking with Mycobacterium tuberculosis kinases A and B (PDB code: 6B2P) and validated by molecular dynamics simulations to elucidate the most stable drug–protein interactions. Additionally, the MM-PBSA analysis shows that the strongest binding occurs in complexes X3, X4, and X6 with ΔGbind values of −8.2, −15.3, and −12.0 kcal/mol, respectively. Our in silico study aims to prospect these new anti-tubercular drugs and their potential development through perspective in vitro and in vivo assays. Full article
(This article belongs to the Section Molecular Biophysics)
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21 pages, 6342 KiB  
Article
Nanostructured Coatings for Spinal Fixation Screws: A Dual-Function Approach Against Biofilm Formation and Implant Failure
by Tiberiu Gabriel Panaitescu, Adelina-Gabriela Niculescu, Valentina Grumezescu, Bogdan Costăchescu, Alexandra Cătălina Bircă, Paul Cătălin Balaure, Ovidiu Cristian Oprea, Ionela Cristina Voinea, Miruna S. Stan, Alina Maria Holban, Bogdan Ștefan Vasile, Alexandru Mihai Grumezescu and Daniel Mihai Teleanu
Coatings 2025, 15(5), 584; https://doi.org/10.3390/coatings15050584 - 14 May 2025
Cited by 1 | Viewed by 718
Abstract
Implant-associated infections represent challenging complications following orthopedic surgeries, with spinal fixation procedures being particularly linked with increased risks. Thus, urgent research is required to develop enhanced solutions to avoid bacterial colonization, associated implant failure, and severe issues. Our study is based on the [...] Read more.
Implant-associated infections represent challenging complications following orthopedic surgeries, with spinal fixation procedures being particularly linked with increased risks. Thus, urgent research is required to develop enhanced solutions to avoid bacterial colonization, associated implant failure, and severe issues. Our study is based on the laser coating of surfaces with a composite mixture of PLA/Fe3O4@CEF that can fight against infectious agents and preserve their activity for a prolonged time. In the present study, we synthesized Fe3O4@Ceftriaxone (CEF) nanoparticles by co-precipitation and blended them into polylactic acid (PLA)-based coatings that were thoroughly evaluated from physicochemical and biological points of view. The novelty of this work is the dual functionality of these coatings, combining localized, sustained antibiotic delivery with enhanced biocompatibility for spinal screw applications. The coatings exhibited substantial anti-biofilm effects, reducing Staphylococcus aureus colonization from 1.8 × 108 to 1.6 × 105 CFU/mL and Pseudomonas aeruginosa from 1.2 × 1011 to 1.9 × 106 CFU/mL after 24 h. Furthermore, in vitro assays with murine preosteoblasts and human osteoblasts demonstrated excellent biocompatibility, maintaining >95% cell viability and showing no significant cytotoxicity or inflammatory response. These results highlight the potential of PLA/Fe3O4@CEF composite coatings in preventing implant-associated infections and promoting osseointegration, offering a multifunctional strategy for improving spinal fixation screw longevity and patient outcomes. Full article
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25 pages, 11534 KiB  
Article
Repurposing Mouthwashes: Antifungal and Antibiofilm Abilities of Commercially Available Mouthwashes Against Candida spp.
by Marie Maziere, Paulo Rompante, José Carlos Andrade, Beatriz S. F. De Oliveira, Mariana C. Alves and Celia Fortuna Rodrigues
Antibiotics 2025, 14(5), 483; https://doi.org/10.3390/antibiotics14050483 - 9 May 2025
Viewed by 977
Abstract
Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather [...] Read more.
Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather in unlocking the untapped potential of existing substances. Materials and Methods: Eighteen mouthwashes, chosen based on their composition, were tested in vitro against ten Candida strains, including clinical isolates of oral origin and reference strains, in both planktonic and biofilm forms. The antifungal susceptibility testing was conducted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion method and the evaluation of the kinetic growth in planktonic Candida. Biofilm reduction was determined by the evaluation of the minimal biofilm eradication concentration (MBEC). Scanning electron microscopy (SEM) analysis was performed to evaluate potential morphological alterations of Candida biofilms. Results: Most mouthwashes effectively reduced biomass production and colony-forming unit (CFU) count. Parodontax Extra showed the highest efficacy. In the disc diffusion assay, Gum Paroex 0.12% exhibited the largest average inhibition zone diameter. Some unusual trends in the data may be explained by a higher reaction of fungal cells and the release of excess biomass during co-incubation in higher concentration of mouthwashes. SEM images revealed significant morphological alterations. Conclusion: Mouthwashes containing chlorhexidine digluconate, either alone or in combination with cetylpyridinium chloride and other active compounds, emerged as a common factor among the most efficacious formulations. In vivo studies will be essential to validate these findings, but mouthwashes may serve as a valuable adjuvant in the treatment of oral candidiasis. Full article
(This article belongs to the Special Issue Microbial Biofilms: Identification, Resistance and Novel Drugs)
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20 pages, 3927 KiB  
Article
Antimicrobial Activity, Genetic Diversity and Safety Assessment of Lactic Acid Bacteria Isolated from European Hakes (Merluccius merluccius, L.) Caught in the Northeast Atlantic Ocean
by Lara Díaz-Formoso, Diogo Contente, Javier Feito, Belén Orgaz, Pablo E. Hernández, Juan Borrero, Estefanía Muñoz-Atienza and Luis M. Cintas
Antibiotics 2025, 14(5), 469; https://doi.org/10.3390/antibiotics14050469 - 6 May 2025
Viewed by 802
Abstract
Background/Objectives: The overuse and misuse of antibiotics has contributed significatively to the growing problem of the emergence and spread of antibiotic resistance genes among bacteria, posing a serious global challenge to the treatment of bacterial infectious diseases. For these reasons, there is a [...] Read more.
Background/Objectives: The overuse and misuse of antibiotics has contributed significatively to the growing problem of the emergence and spread of antibiotic resistance genes among bacteria, posing a serious global challenge to the treatment of bacterial infectious diseases. For these reasons, there is a current and growing interest in the development of effective alternative or complementary strategies to antibiotic therapy for the prevention of fish diseases, which are mainly based on the use of probiotics—in particular, those belonging to the Lactic Acid Bacteria (LAB) group. In this context, the aim of the present study was to characterise, evaluate the genetic diversity and assess the safety of candidate probiotic LAB strains for aquaculture isolated from faeces and intestines of European hakes (Merluccius merluccius, L.) caught in the Northeast Atlantic Ocean (Ireland). Methods: The direct antimicrobial activity of the LAB isolates was tested by the Stab-On-Agar method against key ichthyopathogens. Subsequently, their taxonomic classification and genetic diversity were determined by 16SrDNA sequencing and Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR), respectively. To ensure the in vitro safety of the LAB isolates, their biofilm-forming ability was assessed by a microtiter plate assay; their sensitivity to major antibiotics used in aquaculture, human and veterinary medicine by a broth microdilution method and their haemolytic and gelatinase activity by microbiological assays. Results: All LAB isolates were biofilm producers and susceptible to chloramphenicol, oxytetracycline, flumequine and amoxicillin. A total of 30 isolates (85.7%) were resistant to at least one of the tested antibiotics. None of the 35 LAB isolates showed haemolytic or proteolytic activity. Conclusions: Among the isolated strains, five LAB strains exhibiting the highest antimicrobial activity against aquaculture-relevant ichthyopathogens, taxonomically identified as Streptococcus salivarius, Enterococcus avium and Latilactobacillus sakei, were selected for further characterisation as potential probiotic candidates to promote sustainable aquaculture. To our knowledge, this is the first study to report that hake intestines and faeces represent viable ecological niches for the isolation of LAB strains with antimicrobial activity. Full article
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14 pages, 3718 KiB  
Article
Scalable Production of Recombinant Adeno-Associated Virus Vectors Expressing Soluble Viral Receptors for Broad-Spectrum Inhibition of Porcine Reproductive and Respiratory Syndrome Virus Type 2
by Xiaoming Liu, Nuo Xu, Xiaoli Song, Linlin Zhuang, Qiuping Shen and Huaichang Sun
Vet. Sci. 2025, 12(4), 366; https://doi.org/10.3390/vetsci12040366 - 14 Apr 2025
Viewed by 629
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a major threat to the global swine industry, causing significant economic losses. To address this, we developed a scalable recombinant adeno-associated virus (rAAV)-based strategy for the delivery of soluble viral receptors (SVRs) to [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a major threat to the global swine industry, causing significant economic losses. To address this, we developed a scalable recombinant adeno-associated virus (rAAV)-based strategy for the delivery of soluble viral receptors (SVRs) to treat and potentially eliminate PRRSV infections. This strategy involves fusing the virus-binding domains of two key cellular receptors, sialoadhesin (Sn4D) and CD163 (SRCR5-9), with an Fc fragment. We then used an insect cell–baculovirus expression vector system to produce the rAAV-SRCR59-Fc/Sn4D-Fc vector. Through a series of optimizations, we determined the best conditions for rAAV production, including a baculovirus co-infection ratio of 0.5:1.0, an initial insect cell density of 2.0 × 106 cells/mL, a fetal bovine serum concentration of 2%, and a culture temperature of 30 °C. Under these optimized conditions, we achieved a high titer of rAAV-SRCR59-Fc/Sn4D-Fc in a 2 L bioreactor, reaching 5.4 ± 0.9 × 109 infectious viral particles (IVPs)/mL. Notably, in vitro neutralization assays using a Transwell co-culture system demonstrated a 4.3 log reduction in viral titers across genetically diverse PRRSV-2 strains, including VR2332, JXA1, JS07, and SH1705. Collectively, this study provides a robust platform for large-scale rAAV production and highlights the potential of SVR-based gene therapy to address the antigenic diversity of PRRSV-2. Full article
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23 pages, 3549 KiB  
Article
Efavirenz Repurposing Challenges: A Novel Nanomicelle-Based Antiviral Therapy Against Mosquito-Borne Flaviviruses
by Sofía Maldonado, Pedro Fuentes, Ezequiel Bernabeu, Facundo Bertera, Javier Opezzo, Eduardo Lagomarsino, Hyun J. Lee, Fleming Martínez Rodríguez, Marcelo R. Choi, María Jimena Salgueiro, Elsa B. Damonte, Christian Höcht, Marcela A. Moretton, Claudia S. Sepúlveda and Diego A. Chiappetta
Pharmaceutics 2025, 17(2), 241; https://doi.org/10.3390/pharmaceutics17020241 - 12 Feb 2025
Viewed by 1039
Abstract
Background/Objective: World Health Organization latest statistics state that 17% of infectious diseases are transmitted by vectors, causing more than 700,000 deaths each year. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infections have generated international awareness due to their epidemic proportion [...] Read more.
Background/Objective: World Health Organization latest statistics state that 17% of infectious diseases are transmitted by vectors, causing more than 700,000 deaths each year. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infections have generated international awareness due to their epidemic proportion and risks of international spread. In this framework, the repositioning strategy of Efavirenz (EFV) represents a key clinical feature to improve different antiviral therapies. Therefore, the development of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) for optimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated. Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size and in vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitro cytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviral activity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histological studies were assessed in Wistar rats. Results: EFV encapsulation within Soluplus® NMs increased the drug’s apparent aqueous solubility up to 4803-fold with a unimodal micellar size distribution and a micellar size of ~90 nm at 25 and 37 °C. Micellar in vitro interaction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellar physicochemical stability at 4 °C was confirmed over 2 years. In vitro cytocompatibility assays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safe nanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitro antiviral activity compared with EFV solution for all the tested flaviviruses. In addition, the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably more biological efficacy compared to EFV solution in A549 and Vero cell lines and for each viral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhanced after the oral administration of EFV-loaded NMs, being biocompatible by not causing damage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulation highlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV and YFV antiviral therapy. Full article
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19 pages, 1749 KiB  
Article
In Vitro Determination of Antimicrobial, Antioxidant and Antiviral Properties of Greek Plant Extracts
by Aliki Tsakni, Eirini Kyriakopoulou, Sophia Letsiou, Panagiotis Halvatsiotis, Haralambos Rigopoulos, Niki Vassilaki and Dimitra Houhoula
Microorganisms 2025, 13(1), 177; https://doi.org/10.3390/microorganisms13010177 - 16 Jan 2025
Cited by 2 | Viewed by 1983
Abstract
The medicinal potential of plant extracts, especially their antimicrobial, antioxidant, antiviral and cytotoxic properties, has gained significant attention in recent years. This study examined the in vitro bioactivities of several selected Greek medicinal plants, like Eucalyptus globulus L., Thymus vulgaris L., Salvia rosmarinus [...] Read more.
The medicinal potential of plant extracts, especially their antimicrobial, antioxidant, antiviral and cytotoxic properties, has gained significant attention in recent years. This study examined the in vitro bioactivities of several selected Greek medicinal plants, like Eucalyptus globulus L., Thymus vulgaris L., Salvia rosmarinus L. and Ocimum basilicum L., are well-known for their traditional therapeutic use. Minimum inhibitory concentration (MIC) assays were used to evaluate the antimicrobial activity of the extracts against pathogenic bacteria. The antioxidant activity was carried out using the DPPH method, while the cytotoxicity of the plants was determined using the Alamar Blue method. In addition, the antiviral efficacy of the samples was tested against DENV in different cell lines. The majority of medicinal herbs demonstrated significant antimicrobial action (MIC = 30–3000 μg∙mL−1). The extracts showed great antioxidant activity, while the Salvia rosmarinus L. extract turned out to be the most effective (IC50 = 12.89 ± 0.11 μg∙mL−1). In contrast, the extract of Eucalyptus globulus L. had the lowest antioxidant action (IC50 = 71.02 ± 0.42 μg∙mL−1). The results of the Alamar Blue method were presented with CC50 values, and it was shown that Eucalyptus globulus L. extract exhibited the highest cytotoxicity (CC50 = 5.94% v/v ± 0.04). Similarly, the results of the antiviral potential of extracts were expressed as EC50 values, and Eucalyptus globulus L. was characterized as the most effective sample against dengue virus infection, with EC50 values estimated at 2.37% v/v ± 0.6 (HuhD-2 cells infected with DENV-2) and 0.36% v/v ± 0.004 (Huh7.5 cells infected with DVR2A). These findings provide a foundation for further studies in order to combat infectious diseases and promote human health. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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18 pages, 2881 KiB  
Article
A Screen of Traditional Chinese Medicinal Plant Extracts Reveals 17 Species with Antimicrobial Properties
by Garrett L. Ellward, Macie E. Binda, Dominika I. Dzurny, Michael J. Bucher, Wren R. Dees and Daniel M. Czyż
Antibiotics 2024, 13(12), 1220; https://doi.org/10.3390/antibiotics13121220 - 17 Dec 2024
Cited by 2 | Viewed by 2626
Abstract
Background/Objectives: Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global health and economic security. Many clinical isolates of these pathogens have become completely resistant to current antibiotics, making treatment nearly impossible. Herbal remedies, such as those found in Traditional Chinese Medicine (TCM), have been practiced for thousands of years and successfully used to treat a wide range of ailments, including infectious diseases. Surprisingly, despite this extensive knowledge of folk medicine, no plant-derived antibacterial drugs are currently approved for clinical use. As such, the objective of this study is to evaluate the antimicrobial properties of extracts derived from TCM plants. Methods: This study explores a comprehensive library comprising 664 extracts from 132 distinct TCM plant species for antimicrobial properties against gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria using liquid and solid in vitro assays. Results: Intriguingly, our results reveal 17 plant species with potent antimicrobial properties effective primarily against gram-positive organisms, including Streptococcus aureus and epidermidis. A literature search revealed that nearly 100 purified compounds from the identified TCM plants were previously isolated and confirmed for their antimicrobial properties, collectively inhibiting 45 different bacterial species. Conclusions: Our results indicate that phytobiotics from the identified plants could serve as potential candidates for novel antimicrobials. Full article
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18 pages, 2215 KiB  
Article
Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation
by Aanand Sonawane, Deepak Selvam, Ling Yue, Manohar Nesakumar, Sandhya Vivekanandan, Manickam Ashokkumar, Eric Hunter and Luke Elizabeth Hanna
Viruses 2024, 16(12), 1854; https://doi.org/10.3390/v16121854 - 29 Nov 2024
Viewed by 1242
Abstract
The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this [...] Read more.
The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants. All the clones were characterized genotypically through whole genome sequencing and phenotypically for infectivity, replication kinetics, co-receptor usage, as well as their susceptibility to neutralizing antibodies and entry inhibitors using standard virological assays. Genotypic analysis revealed that all the T/F clones were of non-recombinant subtype C, but some of them harboured the Y181C drug resistance mutation associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretroviral drugs. In vitro studies showed that while all the IMCs were capable of replicating in PBMCs and utilized the CCR5 co-receptor for cellular entry, the drug-resistant variants had significantly lower replicative capacity and per particle infectivity than the drug-sensitive viruses. Both exhibited similar sensitivities to a standard panel of broadly neutralizing monoclonal antibodies and viral entry inhibitors. These findings suggest that despite their diminished replicative fitness, the drug-resistant T/F variants retain transmission fitness and remain susceptible to neutralizing antibody-based interventions and viral entry inhibitors. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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11 pages, 7411 KiB  
Article
Small Molecule Inhibitors of Mycobacterium tuberculosis Topoisomerase I Identified by Machine Learning and In Vitro Assays
by Somaia Haque Chadni, Matthew A. Young, Pedro Igorra, Md Anisur Rahman Bhuiyan, Victor Kenyon and Yuk-Ching Tse-Dinh
Int. J. Mol. Sci. 2024, 25(22), 12265; https://doi.org/10.3390/ijms252212265 - 15 Nov 2024
Cited by 1 | Viewed by 1506
Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a leading infectious cause of death globally. The treatment of patients becomes much more difficult for the increasingly common multi-drug resistant TB. Topoisomerase I is essential for the viability of M. tuberculosis and has been validated [...] Read more.
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a leading infectious cause of death globally. The treatment of patients becomes much more difficult for the increasingly common multi-drug resistant TB. Topoisomerase I is essential for the viability of M. tuberculosis and has been validated as a new target for the discovery of novel treatment against TB resistant to the currently available drugs. Virtual high-throughput screening based on machine learning was used in this study to identify small molecules that target the binding site of divalent ion near the catalytic tyrosine of M. tuberculosis topoisomerase I. From the virtual screening of more than 2 million commercially available compounds, 96 compounds were selected for testing in topoisomerase I relaxation activity assay. The top hit that has IC50 of 7 µM was further investigated. Commercially available analogs of the top hit were purchased and tested with the in vitro enzyme assay to gain further insights into the molecular scaffold required for topoisomerase inhibition. Results from this project demonstrated that novel small molecule inhibitors of bacterial topoisomerase I can be identified starting with the machine-learning-based virtual screening approach. Full article
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15 pages, 1010 KiB  
Review
Emerging Technologies for the Assessment of Natural Killer Cell Activity
by Anna Luise Grab and Alexander Nesterov-Müller
J 2024, 7(4), 457-471; https://doi.org/10.3390/j7040027 - 7 Nov 2024
Viewed by 2043
Abstract
Understanding natural killer (NK) cell functionality is essential in developing more effective immunotherapeutic strategies that can enhance patient outcomes, especially in the context of cancer treatment. This review provides a comprehensive overview of both traditional and novel techniques for evaluating NK cell functionality, [...] Read more.
Understanding natural killer (NK) cell functionality is essential in developing more effective immunotherapeutic strategies that can enhance patient outcomes, especially in the context of cancer treatment. This review provides a comprehensive overview of both traditional and novel techniques for evaluating NK cell functionality, focusing on multiparameter assays and spatial methods that illuminate NK cell interactions within their microenvironment. We discuss the significance of standardized assays for assessing NK cell function across various research and clinical settings, including cancer immunotherapy, infectious diseases, and transplantation. Key factors influencing NK cell functionality include the origin of the sample, target–effector ratios, the functional state of NK cells, and the impact of pre-treatment conditions and their natural aging effect on NK cell activity. By emphasizing the importance of selecting a suitable technique for reliable measurements, especially for longitudinal monitoring, this review aims to give an overview on techniques to measure NK cell functionality in vitro and show the interaction with their microenvironment cells by spatial imaging. Ultimately, our understanding of NK cell functionality could be critical to biomarker development, drug design, and understanding of disease progression in the field of oncology or infectious disease. Full article
(This article belongs to the Section Medicine & Pharmacology)
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16 pages, 3261 KiB  
Article
Antiviral Potential of Chiococca alba (L.) Hitchc. Plant Extracts Against Chikungunya and Mayaro Viruses
by Ellen Caroline Feitoza Pires, Francini Pereira da Silva, Karoline Schallenberger, Bruna Saraiva Hermann, Larissa Mallmann, Wellington Souza Moura, Sergio Donizeti Ascêncio, Robson dos Santos Barbosa, Ilsamar Mendes Soares, Juliane Deise Fleck, Eugênio Eduardo de Oliveira, Guy Smagghe, Bergmann Morais Ribeiro and Raimundo Wagner de Souza Aguiar
Int. J. Mol. Sci. 2024, 25(21), 11397; https://doi.org/10.3390/ijms252111397 - 23 Oct 2024
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Abstract
Chikungunya and Mayaro fevers are viral infectious diseases characterized by fever and arthralgia, for which there are currently no effective vaccines or treatments. The urgent need for novel antiviral agents against Chikungunya virus (CHIKV) and Mayaro virus (MAYV) has led to interest in [...] Read more.
Chikungunya and Mayaro fevers are viral infectious diseases characterized by fever and arthralgia, for which there are currently no effective vaccines or treatments. The urgent need for novel antiviral agents against Chikungunya virus (CHIKV) and Mayaro virus (MAYV) has led to interest in plant-based compounds that can disrupt the viral replication cycle. Chiococca alba (L.) Hitchc., a Neotropical plant traditionally used by Yucatec Maya healers as an antipyretic and antirheumatic, may hold potential as a source of antiviral agents. This study aimed to evaluate the antiviral potential of C. alba methanolic extracts (CAH21 and CAH24) against CHIKV and MAYV through preliminary in vitro and in silico analyses. The cytotoxicity of two methanolic extracts from C. alba roots was assessed in Vero cells using the neutral red assay, and their viral activity was determined via plaque assay post-treatment. Given the observed antiviral effects, we used computational predictions to explore interactions between the multifunctional nsP2 proteases and secondary metabolites identified in C. alba extracts. The metabolites were identified using high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS). Phytochemical analysis revealed the presence of flavonoids, coumarins, and phenolic acids in the C. alba extracts. In vitro assays demonstrated that both extracts inhibited over 70% of activity against CHIKV and MAYV at a concentration of 60 µg/mL. In silico predictions suggested that the flavonoids naringin and vitexin had the highest affinity for the nsP2 proteases of CHIKV and MAYV, indicating their potential as viral inhibitors. Our findings revealed that C. alba extract represents a promising source of novel antiviral compounds. Full article
(This article belongs to the Section Molecular Plant Sciences)
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