Search Results (986)

SARS-CoV-2 undergoes frequent mutations that drive viral evolution and genomic diversity, influencing transmissibility, immune escape, and disease severity. In this study, we performed whole-genome sequencing on SARS-CoV-2 isolates from patients in New York City and identified several globally rare mutations across multiple viral lineages. The isolates analyzed for rare mutations belonged to three lineages: B.1.1.7 (Alpha), B.1.526 (Iota), and B.1.623. We identified 16 rare mutations (global incidence <1000) in non-structural protein genes, including nsp2, nsp3, nsp4, nsp6, nsp8, nsp13, nsp14, ORF7a, and ORF8. Three of these mutations—located in nsp2, nsp13, and ORF8—have been reported in fewer than 100 individuals worldwide. We also detected five rare mutations in structural proteins (S, M, and N), including two—one in M and one in N—previously reported in fewer than 100 cases globally. We present clinical profiles of three patients, each infected with genetically distinct viral isolates from the three lineages studied. Furthermore, we illustrate a local transmission chain inferred from unique mutation patterns identified in the Omicron genome. These findings underscore the importance of whole-genome sequencing for detecting rare mutations, tracking community spread, and identifying emerging variants with clinical and public health significance. Full article

Insects and their bacterial endosymbionts form intricate ecological relationships, yet their role in host–pathogen interactions are not fully elucidated. The small brown planthopper (Laodelphax striatellus), a polyphagous pest of cereal crops, acts as a key vector for rice stripe virus (RSV), a significant threat to rice production. This study aimed to compare the endosymbiont community structures of nonviruliferous and RSV-viruliferous L. striatellus populations using 16S rRNA gene sequencing with high-throughput sequencing technology. Wolbachia was highly dominant in both groups; however, the prevalence of other endosymbionts, specifically Rickettsia and Burkholderia, differed markedly depending on RSV infection. Comprehensive microbial diversity and composition analyses revealed distinct community structures between nonviruliferous and RSV-viruliferous populations, highlighting potential interactions and implications for vector competence and virus transmission dynamics. These findings contribute to understanding virus-insect-endosymbiont dynamics and could inform strategies to mitigate viral spread by targeting symbiotic bacteria. Full article

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

Background/Objectives: Saliva as a diagnostic medium for COVID-19 requires fewer resources to collect and is more readily adopted across a range of testers. Our study compared an Emergency Use Authorized direct saliva-to-RT-qPCR test against an FDA-authorized nasal swab RT-qPCR assay for participants who reported symptoms of respiratory infection. Methods: We analyzed 737 symptomatic participants who self-selected to test at either a community testing facility or a walk-in clinic due to respiratory symptoms and provided matched saliva and nasal swab samples. Samples were collected between March and September of 2023, both before and after the declared end of the public health emergency. Results: A total of 120 participants tested positive in at least one of the tests. For participants testing in the first 5 days of reported symptoms, the saliva test had a 94.0 positive percent agreement (PPA; 95% C.I. 88.9–99.1%) with the nasal test and a 99.0 negative percent agreement (NPA; 95% C.I. 98.1–99.9%). The viral load decreased beyond day 1 of reported symptoms for saliva testing. Viral load increased up to day 4 for nasal swabs and then decreased. The same number of discordant positive samples (five each) occurred for both tests within 5 days of symptoms onset. Conclusions: In the endemic phase of COVID-19 and for development of new tests, testing methods that are less invasive are more likely to be adopted. The results of saliva-based versus nasal swab PCR measurements relative to days of symptom onset are needed to optimize future testing strategies. Full article

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies—metagenomics, metatranscriptomics, metaproteomics, and metabolomics—offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin–microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases. Full article

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

Background/Objectives: Mpox re-emerged in 2022 as a global health concern. Between 2022 and 2025, Portugal experienced three distinct outbreak waves, highlighting the critical role of laboratory surveillance and public health interventions. This study describes the epidemiological trends, diagnostic performance, and key lessons learned to improve outbreak preparedness. Methods: A total of 5610 clinical samples from 2802 suspected cases were analyzed at the National Institute of Health Doutor Ricardo Jorge using real-time PCR methods. Positivity rates and viral loads (Ct values) were assessed across different clinical specimen types, including lesion, anal, oropharyngeal swabs, and urine samples. Results: Mpox was confirmed in 1202 patients. The first outbreak accounted for 79.3% of cases (n = 953), followed by a significant reduction in transmission during subsequent waves. Lesion and rectal swabs provided the highest diagnostic sensitivity (95.1% and 87.9%, respectively). Oropharyngeal swabs contributed to diagnosis in cases without visible lesions, while urine samples showed limited utility. Conclusions: This study underscores the importance of sustained laboratory surveillance and adaptive public health strategies in controlling mpox outbreaks. Optimizing specimen collection enhances diagnostic accuracy, supporting early detection. Continuous monitoring, combined with targeted vaccination and effective risk communication, is essential to prevent resurgence and ensure rapid response in non-endemic regions. Full article

Background/Objective: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with unclear etiology. Increasing evidence implicates oral microbial dysbiosis in its pathogenesis, but little is known about supragingival plaque communities in relation to clinical subtypes. This cross-sectional case–control study aimed to characterize the supragingival plaque microbiota and microbial interaction networks in erosive OLP (E-OLP), non-erosive OLP (NE-OLP), and healthy controls (HCs), to elucidate microbial patterns associated with disease severity. Methods: Supragingival plaque samples were collected from 90 participants (30 per group) and analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance, and co-occurrence network analyses were performed. Results: E-OLP exhibited pronounced dysbiosis, including the enrichment of pro-inflammatory taxa (e.g., Prevotella, Parvimonas) and depletion of health-associated commensals (e.g., Rothia, Capnocytophaga). Network analysis revealed the stepwise disintegration of microbial community structure from HC to NE-OLP to E-OLP, with reduced connectivity and increased dominance of pathogenic clusters in E-OLP. These microbial alterations aligned with clinical findings, as E-OLP patients showed significantly higher Reticulation/keratosis, Erythema, and Ulceration (REU) scores for erythema and ulceration compared to NE-OLP. Conclusions: Supragingival plaque dysbiosis and ecological disruption are strongly associated with OLP severity and subtype. This study highlights the utility of plaque-based microbial profiling in capturing lesion-proximal dysbiotic signals, which may complement mucosal and salivary analyses in future diagnostic frameworks. Multi-omics approaches incorporating fungal, viral, and metabolic profiling are warranted to fully elucidate host–microbe interactions in OLP. Full article

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

The recent COVID-19 pandemic has prompted the scientific community to prioritize the discovery of preventive methods and new therapeutics, including the investigation of natural compounds with antiviral potential. Fungal secondary metabolites (SMs) represent a promising source of antiviral drugs due to their structural diversity and intrinsic biocompatibility. Herein, the antiviral activity of 6-pentyl-α-pyrone (6PP) against bovine coronavirus (BCoV) has been evaluated in vitro. Considering that BCoV and SARS-CoV-2 are both members of the Betacoronavirus genus and share several key features, BCoV represents a valuable reference model for human coronavirus research. A non-cytotoxic dose of 6PP was used on MDBK cells to evaluate its antiviral activity against BCoV. Different experimental conditions were employed to examine cell monolayer protection both pre- and post-infection, as well as the potential inhibition of viral internalization. Overall, post-infection 6PP treatment reduced viral load and decreased viral internalization. Results were analyzed using viral titration and quantitative PCR, while data interpretation was performed by statistical software tools. This study presents a novel fluorescence quantification approach with high confidence demonstrated by its significant concordance with RT-qPCR results. These data suggest that 6PP could be an effective antiviral agent for BCoV, warranting further investigation of its role in coronavirus inhibition. Full article

Hepatobiliary diseases, which include disorders of the liver, gallbladder, and bile ducts, remain a major global health concern. A significant proportion of deaths worldwide are attributed to hepatic diseases, accounting for 4% of the total global mortality in 2023. Among benign hepatobiliary diseases, metabolic dysfunction-associated steatotic liver disease is the most prevalent liver pathology, with a concerning rise in incidence, while it is recognized as the leading cause of liver transplantation in the United States. However, there is a notable rise over time in cases of autoimmune hepatobiliary disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Meanwhile, hepatocellular carcinoma still remains the most frequently diagnosed hepatobiliary malignancy, constituting the third leading cause of malignancy-related mortality globally. Meanwhile, cholangiocarcinoma and gallbladder cancer are the second and third most common hepatobiliary malignancies, respectively, both exhibiting highly aggressive malignant behavior. Despite the notable advances in biomarkers and the development of therapeutic tools, early diagnosis and monitoring are considered pivotal for the management of the aforementioned pathologies. The development of new non-invasive biomarkers that can effectively identify, monitor these pathologies, and guide their management is considered a necessity. Extracellular vesicles (EVs) constitute nanoparticles with several embedded cargoes, with a significant role in intercellular communication, which are considered promising biomarkers in several diseases, including viral, metabolic, autoimmune, and malignant diseases. In this review, we will shed light on the role of EVs as novel frontiers in hepatobiliary diseases. Full article

The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination, public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global spread among wildlife and domestic animals underscore the urgent need for robust preparedness. International organizations have called for comprehensive pandemic response plans, enhanced multisectoral collaboration, and investment in targeted research. Priorities include expanding surveillance to asymptomatic animal hosts, evaluating viral shedding and transmission routes, and developing strain-specific and universal vaccines. Strengthening global cooperation and public health infrastructure will be critical to mitigate the growing threat of H5N1 and reduce the risk of a future influenza pandemic. Full article

The gut microbiota constitutes a complex community of microorganisms (including bacteria, viruses, fungi, and protozoa) within the intestinal tract. Over the years, an increasing number of studies have highlighted the bidirectional communication between the gut microbiota and the central nervous system (CNS), a relationship commonly referred to as the “microbiota–gut–brain axis”. In particular, the crosstalk between the gut microbiota and the brain has been associated with the pathogenesis and progression of various CNS disorders. Phages, or bacteriophages, viruses that specifically infect bacteria, constitute the most abundant viral component within the gut microbiota. However, despite their abundance and significance in the gut microbial community, studies exploring the relationship between phages and the CNS remain surprisingly limited. This review examines the biological interplay between gut-resident phages and the CNS. Furthermore, we discuss the current literature linking phages to CNS-related pathologies. Full article

Bats serve as key ecological reservoirs of diverse microbial communities, including emerging viruses and antibiotic resistance genes. This study investigates the intestinal microbiota of two insectivorous bat species, Nyctalus noctula and Vespertilio murinus, at the Rostov Bat Rehabilitation Center in Southern Russia using whole metagenome shotgun sequencing. We analyzed taxonomic composition, functional pathways, antibiotic resistance genes, and virulence factors. Densoviruses, especially those closely related to Parus major densovirus, were the most dominant viral sequences identified. Metagenome-assembled densovirus genomes showed high sequence similarity with structural variations and clustered phylogenomically with viruses from mealworms and birds, reflecting both dietary origins and the potential for vertebrate infection. Functional profiling revealed microbial pathways associated with cell wall biosynthesis, energy metabolism, and biofilm formation. A total of 510 antibiotic resistance genes, representing 142 unique types, mainly efflux pumps and β-lactamases, were identified. Additionally, 870 virulence factor genes were detected, with a conserved set of iron acquisition systems and stress response regulators across all samples. These findings highlight the ecological complexity of bat-associated microbiota and viromes and suggest that synanthropic bats may contribute to the circulation of insect-associated viruses and antimicrobial resistance in urban settings. Full article

Equine Herpesvirus Type 1 (EHV-1) is a significant pathogen within the Alphaherpesvirinae subfamily, causing respiratory disease, abortions, and, in severe cases, equine herpesvirus myeloencephalopathy (EHM). While nasal swabs and blood samples are commonly used for real-time polymerase chain reaction (RT-PCR) diagnosis, variability in viral shedding necessitates exploring additional sample types. This study reports the first molecular detection of EHV-1 in ocular swabs from naturally infected horses during an outbreak in the Valencian Community in 2023. Nasal and ocular swabs were collected from ten symptomatic horses and analyzed via RT-PCR. EHV-1 was detected in all cases, with higher viral loads in nasal samples. Although nasal swabs remain the most reliable sample for EHV-1 detection, the presence of viral DNA in tear fluid suggests a previously unrecognized route of viral shedding. These findings support further investigation into the role of ocular secretions in the pathogenesis and epidemiology of EHV-1. Additional studies are needed to determine the clinical relevance and potential utility of ocular swabs in specific outbreak scenarios. Full article