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26 pages, 3951 KiB  
Article
Exploring the Bioactive Potential and Chemical Profile of Schinus molle Essential Oil: An Integrated In Silico and In Vitro Evaluation
by Rómulo Oses, Matías Ferrando, Flavia Bruna, Patricio Retamales, Myriam Navarro, Katia Fernández, Waleska Vera, María José Larrazábal, Iván Neira, Adrián Paredes, Manuel Osorio, Osvaldo Yáñez, Martina Jacobs and Jessica Bravo
Plants 2025, 14(15), 2449; https://doi.org/10.3390/plants14152449 - 7 Aug 2025
Abstract
Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract [...] Read more.
Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL−1). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article
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17 pages, 7335 KiB  
Article
Osage Orange (Maclura pomifera) and Spearmint (Mentha spicata) Leaf Extracts Exhibit Antibacterial Activity and Inhibit Human Respiratory Syncytial Virus (hRSV)
by Milica Nenadovich, Molly Kubal, Maci R. Hopp, Abigail D. Crawford, Megan E. Hardewig, Madison G. Sedlock, Rida Jawad, Zarrar A. Khan, Adrianna M. Smith, Mia A. Mroueh, Matthew DuBrava, Ellie C. Jones, Cael Rahe, Sean T. Berthrong, Anne M. Wilson, Michael P. Trombley, Ashlee H. Tietje and Christopher C. Stobart
Pathogens 2025, 14(8), 776; https://doi.org/10.3390/pathogens14080776 - 5 Aug 2025
Abstract
The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous [...] Read more.
The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC50 = 1.01 mg/mL) compared to Osage orange (EC50 = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article
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16 pages, 1302 KiB  
Article
Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors
by Ching-Hsuan Liu, Yu-Ting Kuo, Chien-Ju Lin, Feng-Lin Yen, Shu-Jing Wu and Liang-Tzung Lin
Viruses 2025, 17(8), 1086; https://doi.org/10.3390/v17081086 - 5 Aug 2025
Abstract
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, [...] Read more.
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article
(This article belongs to the Section Coronaviruses)
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38 pages, 9437 KiB  
Review
Antibacterial Polysaccharides in Dental Implantology
by Lubica Hallmann and Mark Daniel Gerngroß
Mar. Drugs 2025, 23(8), 321; https://doi.org/10.3390/md23080321 - 4 Aug 2025
Viewed by 238
Abstract
Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used [...] Read more.
Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used to search for peer-reviewed scientific publications published between 2018 and 2025 that provide insights to answer research questions on the role of antibacterial polysaccharides in combating pathogens in dental implantology without triggering immune reactions and inflammation. Further research questions relate to the efficacy against various dental pathogens and the understanding of the antibacterial mechanism, which may enable the development of functionalized polysaccharides with long-term antibacterial activity. Results: Biomedical implants have revolutionized medicine but also increased the risk of infections. Implant infections are a major problem in implantology and lead to implant failure and replacement. An antibacterial coating could be an excellent strategy to extend the lifespan of implants and improve the quality of the patient’s life. Bacterial resistance to antibiotics poses significant challenges for researchers, forcing them to search for new ways to prevent bacterial infections in implantology. Antibacterial natural polymers have recently received considerable research attention due to their long-term antibacterial activity. Polysaccharides from marine sources, such as chitosan and alginate, or pectin, xanthan, etc., from various plants, appear to be promising biopolymers for such applications in implantology due to their antibacterial activity, biocompatibility, and osteogenic properties. The antibacterial activity of these natural biopolymers depends on their chemical and physical properties. Nanopolysaccharides exhibit higher antibacterial activity than conventional polysaccharides, but their toxicity to human cells must be considered. Their antibacterial activity is based on the disruption of bacterial DNA or RNA synthesis, increased cell wall permeability, membrane disruption, and cytoplasmic leakage. Conclusions: Polysaccharides are a class of natural polymers with a broad spectrum of biological activities. They exhibit antioxidant, immunomodulatory, anticoagulant, anticancer, anti-inflammatory, antibacterial, and antiviral activity. Furthermore, polysaccharides are non-cytotoxic and exhibit good biocompatibility with osteogenic cells. Bactericidal polysaccharides are attractive new antibacterial materials against implant infections and open up new perspectives in implantology. Full article
(This article belongs to the Special Issue Marine Biomaterials for Dental Applications)
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18 pages, 1812 KiB  
Review
Nanocarriers for Medical Ozone Delivery: A New Therapeutic Strategy
by Manuela Malatesta and Flavia Carton
Nanomaterials 2025, 15(15), 1188; https://doi.org/10.3390/nano15151188 - 3 Aug 2025
Viewed by 235
Abstract
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century [...] Read more.
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O3 doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O3 make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O3 is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O3. In recent years, novel O3 formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O3, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O3 and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O3 through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article
(This article belongs to the Section Biology and Medicines)
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20 pages, 1573 KiB  
Article
Polyvalent Mannuronic Acid-Coated Gold Nanoparticles for Probing Multivalent Lectin–Glycan Interaction and Blocking Virus Infection
by Rahman Basaran, Darshita Budhadev, Eleni Dimitriou, Hannah S. Wootton, Gavin J. Miller, Amy Kempf, Inga Nehlmeier, Stefan Pöhlmann, Yuan Guo and Dejian Zhou
Viruses 2025, 17(8), 1066; https://doi.org/10.3390/v17081066 - 30 Jul 2025
Viewed by 316
Abstract
Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. [...] Read more.
Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC50. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article
(This article belongs to the Special Issue Role of Lectins in Viral Infections and Antiviral Intervention)
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31 pages, 7303 KiB  
Review
Membrane-Targeting Antivirals
by Maxim S. Krasilnikov, Vladislav S. Denisov, Vladimir A. Korshun, Alexey V. Ustinov and Vera A. Alferova
Int. J. Mol. Sci. 2025, 26(15), 7276; https://doi.org/10.3390/ijms26157276 - 28 Jul 2025
Viewed by 283
Abstract
The vast majority of viruses causing human and animal diseases are enveloped—their virions contain an outer lipid bilayer originating from a host cell. Small molecule antivirals targeting the lipid bilayer cover the broadest spectrum of viruses. In this context, we consider the chemical [...] Read more.
The vast majority of viruses causing human and animal diseases are enveloped—their virions contain an outer lipid bilayer originating from a host cell. Small molecule antivirals targeting the lipid bilayer cover the broadest spectrum of viruses. In this context, we consider the chemical nature and mechanisms of action of membrane-targeting antivirals. They can affect virions by (1) physically modulating membrane properties to inhibit fusion of the viral envelope with the cell membrane, (2) physically affecting envelope lipids and proteins leading to membrane damage, pore formation and lysis, (3) causing photochemical damage of unsaturated membrane lipids resulting in integrity loss and fusion arrest. Other membrane-active compounds can target host cell membranes involved in virion’s maturation, coating, and egress (endoplasmic reticulum, Golgi apparatus, and outer membrane) affecting these last stages of viral reproduction. Both virion- and host-targeting membrane-active molecules are promising concepts for broad-spectrum antivirals. A panel of approved antivirals would be a superior weapon to respond to and control emerging disease outbreaks caused by new viral strains and variants. Full article
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33 pages, 2018 KiB  
Review
Biogenic Synthesis of Silver Nanoparticles and Their Diverse Biomedical Applications
by Xiaokun Jiang, Shamma Khan, Adam Dykes, Eugen Stulz and Xunli Zhang
Molecules 2025, 30(15), 3104; https://doi.org/10.3390/molecules30153104 - 24 Jul 2025
Viewed by 545
Abstract
Nanoparticles (NPs) synthesised through biogenic routes have emerged as a sustainable and innovative platform for biomedical applications such as antibacterial, anticancer, antiviral, anti-inflammatory, drug delivery, wound healing, and imaging diagnostics. Among these, silver nanoparticles (AgNPs) have attracted significant attention due to their unique [...] Read more.
Nanoparticles (NPs) synthesised through biogenic routes have emerged as a sustainable and innovative platform for biomedical applications such as antibacterial, anticancer, antiviral, anti-inflammatory, drug delivery, wound healing, and imaging diagnostics. Among these, silver nanoparticles (AgNPs) have attracted significant attention due to their unique physicochemical properties and therapeutic potential. This review examines the biogenic synthesis of AgNPs, focusing on microbial, plant-based, and biomolecule-assisted approaches. It highlights how reaction conditions, such as pH, temperature, and media composition, influence nanoparticle size, shape, and functionality. Particular emphasis is placed on microbial synthesis for its eco-friendly and scalable nature. The mechanisms of AgNP formation and their structural impact on biomedical performance are discussed. Key applications are examined including antimicrobial therapies, cancer treatment, drug delivery, and theranostics. Finally, the review addresses current challenges, such as reproducibility, scalability, morphological control, and biosafety, and outlines future directions for engineering AgNPs with tailored properties, paving the way for sustainable and effective next-generation biomedical solutions. Full article
(This article belongs to the Special Issue Nanomaterials for Advanced Biomedical Applications, 2nd Edition)
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24 pages, 2082 KiB  
Review
Exploring the Pharmacological Landscape of Undaria pinnatifida: Insights into Neuroprotective Actions and Bioactive Constituents
by Helena Machado, Jorge Pereira Machado, Christian Alves, Cristina Soares, Clara Grosso, Jorge Magalhães Rodrigues and Maria Begoña Criado
Nutraceuticals 2025, 5(3), 20; https://doi.org/10.3390/nutraceuticals5030020 - 24 Jul 2025
Viewed by 427
Abstract
The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional [...] Read more.
The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article
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18 pages, 1984 KiB  
Review
Progress on 3-Nitropropionic Acid Derivatives
by Meng-Lin Feng, Zheng-Hui Li and Bao-Bao Shi
Biomolecules 2025, 15(8), 1066; https://doi.org/10.3390/biom15081066 - 24 Jul 2025
Viewed by 310
Abstract
3-Nitropropionic acid (3-NPA) is a deadly neurotoxic nitroalkane found in numerous fungi and leguminous plants. 3-NPA, known as an antimetabolite of succinate, irreversibly inhibits succinate dehydrogenase and disrupts mitochondrial oxidative phosphorylation. Its utility in modeling Huntington’s disease (HD) and oxidative stress has garnered [...] Read more.
3-Nitropropionic acid (3-NPA) is a deadly neurotoxic nitroalkane found in numerous fungi and leguminous plants. 3-NPA, known as an antimetabolite of succinate, irreversibly inhibits succinate dehydrogenase and disrupts mitochondrial oxidative phosphorylation. Its utility in modeling Huntington’s disease (HD) and oxidative stress has garnered significant research interest. Derivatives of 3-NPA, formed through esterification, have a wide range of biological activities including neurotoxic, antiviral, insecticidal, antimicrobial and antioxidant properties. This review systematically summarizes the structural characteristics, biological activities, and chemical synthesis of 3-NPA-derived compounds, providing valuable insights for further research and therapeutic applications. Full article
(This article belongs to the Special Issue Natural Products and Their Derivatives with Antiviral Activity)
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22 pages, 4411 KiB  
Article
Synthesis, Structural Characterization, and In Silico Antiviral Prediction of Novel DyIII-, YIII-, and EuIII-Pyridoxal Helicates
by Francisco Mainardi Martins, Yuri Clemente Andrade Sokolovicz, Morgana Maciél Oliveira, Carlos Serpa, Otávio Augusto Chaves and Davi Fernando Back
Inorganics 2025, 13(8), 252; https://doi.org/10.3390/inorganics13080252 - 23 Jul 2025
Viewed by 450
Abstract
The synthesis and structural characterization of three new triple-stranded helical complexes ([Dy2(L2)3]2Cl∙15H2O (C1), [Y2(L2)3]3(NO3)Cl∙14H2O∙DMSO (C2), and [Eu2(L4) [...] Read more.
The synthesis and structural characterization of three new triple-stranded helical complexes ([Dy2(L2)3]2Cl∙15H2O (C1), [Y2(L2)3]3(NO3)Cl∙14H2O∙DMSO (C2), and [Eu2(L4)3]∙12H2O (C3), where L2 and L4 are ligands derived from pyridoxal hydrochloride and succinic or adipic acid dihydrazides, respectively, were described. The X-ray data, combined with spectroscopic measurements, indicated that L2 and L4 act as bis-tridentate ligands, presenting two tridentate chelating cavities O,N,O to obtain the dinuclear complexes C1C3. Their antiviral profile was predicted via in silico calculations in terms of interaction with the structural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein in the down- and up-states and complexed with the cellular receptor angiotensin-converting enzyme 2 (ACE2). The best affinity energy values (−9.506, −9.348, and −9.170 kJ/mol for C1, C2, and C3, respectively) were obtained for the inorganic complexes docked in the model spike-ACE2, with C1 being suggested as the most promising candidate for a future in vitro validation. The obtained in silico antiviral trend was supported by the prediction of the electronic and physical–chemical properties of the inorganic complexes via the density functional theory (DFT) approach, representing an original and relevant contribution to the bioinorganic and medicinal chemistry fields. Full article
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20 pages, 7204 KiB  
Article
Structural Features and In Vitro Antiviral Activities of Fungal Metabolites Sphaeropsidins A and B Against Bovine Coronavirus
by Luca Del Sorbo, Maria Michela Salvatore, Clementina Acconcia, Rosa Giugliano, Giovanna Fusco, Massimiliano Galdiero, Violetta Iris Vasinioti, Maria Stella Lucente, Paolo Capozza, Annamaria Pratelli, Luigi Russo, Rosa Iacovino, Anna Andolfi and Filomena Fiorito
Int. J. Mol. Sci. 2025, 26(15), 7045; https://doi.org/10.3390/ijms26157045 - 22 Jul 2025
Viewed by 223
Abstract
The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member [...] Read more.
The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection. Full article
(This article belongs to the Special Issue Structure, Function and Dynamics in Proteins: 3rd Edition)
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27 pages, 5867 KiB  
Article
Distinct Virologic Properties of African and Epidemic Zika Virus Strains: The Role of the Envelope Protein in Viral Entry, Immune Activation, and Neuropathogenesis
by Ashkan Roozitalab, Chenyu Zhang, Jiantao Zhang, Ge Li, Chengyu Yang, Wangheng Hou, Qiyi Tang and Richard Y. Zhao
Pathogens 2025, 14(7), 716; https://doi.org/10.3390/pathogens14070716 - 19 Jul 2025
Viewed by 347
Abstract
The 2016 Zika virus (ZIKV) epidemic has largely subsided, but a key question remains. How did ZIKV evolve to become a virulent human pathogen compared to the virus of its original discovery? What specific virologic and pathologic changes contributed to increased pathogenicity in [...] Read more.
The 2016 Zika virus (ZIKV) epidemic has largely subsided, but a key question remains. How did ZIKV evolve to become a virulent human pathogen compared to the virus of its original discovery? What specific virologic and pathologic changes contributed to increased pathogenicity in humans? Phylogenetic studies have identified two genetically distinct ZIKV, the African and Asian lineages, which differ in their pathogenicity. Previous studies including ours suggest that the envelope (E) protein plays a key role in viral entry, immune activation, and neuropathogenesis. This study aimed to further elucidate virologic and pathogenic differences between these lineages by assessing their ability to bind and replicate in host cells, induce apoptotic cell death, trigger inflammatory responses, and influence human neural progenitor cell (hNPC)-derived neurosphere formation. We compared a historic African ZIKV strain (MR766) with an epidemic Brazilian strain (BR15) and evaluated the effects of the E protein inhibitor quercetin-3-β-O-D-glucoside (Q3G) and an E protein-neutralizing antibody (AbII). Our results revealed distinct virologic properties and that MR766 exhibited stronger inhibition of neurosphere formation due to enhanced viral binding to neuronal SH-SY5Y cells, while BR15 infection triggered a heightened pro-inflammatory cytokine response with reduced viral binding. Chimeric virus studies suggested that the E protein likely influences viral binding, replication efficiency, immune activation, and neuropathogenesis. Notably, Q3G exhibited antiviral activities against both MR766 and BR15, whereas AbII preferentially inhibited MR766. These findings highlight the virological differences between ancestral and epidemic viral strains, as well as the critical role of E protein in viral permissiveness, immune response, and neuropathogenesis, providing insights for developing targeted antiviral strategies. Full article
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17 pages, 3046 KiB  
Article
Therapeutic Use of Parerythrobacter sp. M20A3S10, a Marine Bacterium, Targeting Influenza Viruses and Flaviviruses
by Kyeong-Seo Moon, Ji-Young Chung, Hyeon Jeong Moon, Gun Lee, Chung-Do Lee, Su-Bin Jung, Hyo-Jin Kim, Jun-Gyu Park, Yeong-Bin Baek and Sang-Ik Park
Animals 2025, 15(14), 2125; https://doi.org/10.3390/ani15142125 - 18 Jul 2025
Viewed by 271
Abstract
Emerging RNA viruses such as influenza A virus (IAV), Zika virus (ZIKV), and dengue virus (DENV) continue to pose major challenges to animal and public health due to their high mutation rates, wide host ranges, and immune evasion strategies. In this study, we [...] Read more.
Emerging RNA viruses such as influenza A virus (IAV), Zika virus (ZIKV), and dengue virus (DENV) continue to pose major challenges to animal and public health due to their high mutation rates, wide host ranges, and immune evasion strategies. In this study, we evaluated the in vitro antiviral activity of a marine bacterial extract derived from Parerythrobacter sp. M20A3S10 against IAV (H1N1; H3N2), influenza B virus (IBV), ZIKV, and DENV2. The extract demonstrated broad-spectrum antiviral effects with favorable selectivity indices across multiple host-derived epithelial cell lines. Notably, post-infection treatment significantly suppressed viral replication, suggesting a host-modulating or replication-inhibiting mechanism. While the extract’s active components have yet to be identified, bacteria from the Erythrobacteraceae family are known producers of bioactive metabolites with potential antiviral properties. These findings provide preliminary insight into the potential of marine-derived bacterial compounds in veterinary antiviral development and highlight the need for further characterization and in vivo validation. This work contributes to the understanding of virus–host interactions and the exploration of novel therapeutic strategies targeting the pathogenesis and immune modulation of veterinary RNA viruses. Full article
(This article belongs to the Special Issue Pathogenesis, Immunology and Epidemiology of Veterinary Viruses)
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34 pages, 8372 KiB  
Article
Supercomputing Multi-Ligand Modeling, Simulation, Wavelet Analysis and Surface Plasmon Resonance to Develop Novel Combination Drugs: A Case Study of Arbidol and Baicalein Against Main Protease of SARS-CoV-2
by Hong Li, Hailong Su, Akari Komori, Shuxuan Yang, Hailang Luo, Angela Wei Hong Yang, Xiaomin Sun, Hongwei Li, Andrew Hung and Xiaoshan Zhao
Pharmaceuticals 2025, 18(7), 1054; https://doi.org/10.3390/ph18071054 - 17 Jul 2025
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Abstract
Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined [...] Read more.
Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of Mpro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting Mpro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article
(This article belongs to the Special Issue Antiviral Agents, 2024)
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