Search Results (2,500)

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus–host interactions, especially protein–protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction. Full article

The concurrent circulation of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unveiled complex host–pathogen interactions governed by temporal dynamics of innate immune activation. This narrative review synthesizes evidence from human air–liquid interface (ALI) epithelial models, animal studies (hamster, ferret), clinical cohorts, and randomized controlled trials (2015–2026) to delineate the molecular mechanisms underlying viral interference between these two major respiratory pathogens. Prior IAV infection induces a robust type I/III interferon (IFN) response and broad interferon-stimulated gene (ISG) upregulation that restricts subsequent SARS-CoV-2 replication within a critical 24–72 h temporal window. Conversely, SARS-CoV-2 employs a multi-layered immune evasion strategy that blunts IFN induction, providing minimal heterologous protection. Simultaneous co-infection tends to exacerbate disease severity. Host genetic determinants, including OAS1 and TLR7 variants, modulate interference capacity. Therapeutically, early pegylated IFN-λ shows clinical benefit, while experimental evidence from in vitro and animal models suggests oseltamivir may paradoxically reduce IAV-induced interference. These findings underscore the need for multi-pathogen diagnostics, temporally informed clinical decision-making, and IFN-based therapeutic strategies during co-circulation periods. Full article

Bats are important reservoirs of zoonotic pathogens and valuable models for studying antiviral tolerance and neuroinflammation within a One Health framework. However, chiropteran neural 2D-in vitro models remain limited. Here, we established and characterized the first chiropteran primary (CpBCs) and immortalized (CiBCs) cell lines from Hypsugo savii species. To overcome the limited lifespan of CpBCs, immortalization strategies based on human telomerase reverse transcriptase (hTERT) and Simian virus 40 large T antigen (SV40) were evaluated. Electroporation-mediated transfection with SV40 successfully generated CiBCs, whereas liposome-mediated and hTERT-based approaches were unsuccessful. RNA sequencing revealed marked transcriptional changes comparing CiBCs with CpCBs, such as the upregulation of pathways related to cell cycle progression, DNA replication, and proliferation in CiBCs, together with the downregulation of apoptosis, inflammatory signaling, and immune-related pathways. Immortalized cells also exhibited enrichment of neural stem cell-like and cancer-associated signatures, suggesting partial dedifferentiation induced by SV40-mediated immortalization. Overall, this study provides a novel chiropteran brain-derived 2D-in vitro platform for investigating bat neurobiology, host–pathogen interactions, viral tolerance, and neurotropic infectious diseases relevant to emerging zoonoses. Full article

Human norovirus (HuNoV) is the leading cause of foodborne viral gastroenteritis worldwide, yet its persistence in foods is still commonly interpreted through a simplified framework of contamination and residual survival. Accumulating evidence indicates that HuNoV persistence in food systems may be shaped by dynamic, genotype-dependent interactions with multiple classes of candidate ligands and retention mechanisms associated with hosts, food matrices, and microbiota. This review synthesizes current advances in the molecular basis and ecological consequences of these interactions, with emphasis on canonical and non-canonical glycans, HBGA-like substances, proteinaceous ligands, and bacterial surface or matrix-associated components. Structural, biophysical, and food-model studies collectively suggest that such factors may modulate capsid engagement, tissue retention, bioaccumulation, environmental stability, and, in some experimental systems, infectivity-related outcomes in representative matrices including leafy vegetables, bivalve mollusks, and bacteria-rich food environments. This multi-ligand perspective helps explain the matrix-dependent limitations of conventional washing, depuration, disinfection, and nucleic acid-based detection, as well as the frequent disconnect between measured viral signals and actual transmission risk. By linking molecular recognition to real food scenarios, this review highlights a shift from single-receptor and single-treatment perspectives toward mechanism-informed detection, risk assessment, and intervention strategies. A more integrated understanding of virus-ligand-matrix-microbiota interactions will be essential for improving the prediction and control of HuNoV foodborne transmission. Full article

Coronaviruses encode a variety of non-structural proteins (NSPs) that collectively mediate viral genome replication, transcription and remodeling of the host cellular microenvironment. As a highly conserved transmembrane protein, non-structural protein 6 (NSP6) predominantly localizes to the endoplasmic reticulum. Through interactions with other viral proteins and host factors, NSP6 participates in multiple pivotal processes, including the formation and stabilization of double-membrane vesicles (DMVs), reprogramming of lipid metabolism, blockade of autophagic flux, and evasion of innate immunity. Recent advances in structural biology and research on virus–host interactions have further elucidated the essential roles of NSP6 throughout the viral life cycle. Mutations in NSP6 are closely associated with viral adaptability, transmissibility and pathogenicity. Herein, we comprehensively review the latest advances on the molecular structure, biological functions and mutation hotspots of coronavirus NSP6, as well as its implications for antiviral research. This review aims to provide a theoretical basis for further dissecting the pathogenic mechanisms of coronaviruses and developing broad-spectrum antiviral drugs. Full article

Ostreid herpesvirus 1 (OsHV-1) is a major pathogen associated with summer mortality in bivalve mollusks, but the host-side determinants of susceptibility remain poorly characterized outside oysters. In this study, we compared the responses of Chinese (CS) and Korean (KS) populations of the ark clam Scapharca broughtonii to experimental OsHV-1 challenge. The results showed that OsHV-1 established a markedly strong infection in the CS population but not the KS population, as indicated by high viral DNA loads, severe tissue pathology, detection of viral particles by transmission electron microscopy, broad viral transcription, and substantially high mortality. To explore the molecular basis of this contrasting outcome, we further performed comparative transcriptomic and proteomic analyses. Transcriptomic analysis identified two membrane-associated genes, atrial natriuretic peptide receptor A (NPR-A) and tyrosine-protein kinase receptor (TYRO3-like), that were more highly expressed in the susceptible CS population, suggesting that early host–virus interaction may differ between populations as a result of differentially expressed membrane molecules. Proteomic analysis identified 94 differentially abundant proteins between CS and KS populations; notably, ferritin and superoxide dismutase (SOD) were highly expressed in the less susceptible KS population, leading to stronger basal antioxidant and stress-defense capacity. Taken together, these findings definitively confirmed the significant differential susceptibility to OsHV-1 infection between the two S. broughtonii geographic populations and revealed that this divergent phenotype might involve both population-biased expression of candidate membrane-associated factors and differences in defense-related protein abundance. This study provides candidate markers for future disease-resistance evaluation and breeding in ark clam and offers a basis for further investigation of population-level variation in bivalve–virus interactions. Full article

Influenza viruses continue to pose a significant threat to both animal and public health due to their rapid evolution and the frequent emergence of antiviral resistance. Host-directed antiviral (HDA) strategies, which target host factors essential for viral replication, may represent an alternative to conventional virus-targeting approaches. However, the identification of reliable and therapeutically actionable host targets remains a major challenge, primarily due to the complexity and context dependency of host–virus interactions. Recent advancements in multi-omics technologies, including functional genomics, transcriptomics, and proteomics, have facilitated the systematic characterization of host factors involved in influenza virus infection. These methodologies have unveiled intricate regulatory networks that govern viral replication and host immune responses. Nonetheless, translating large-scale datasets into biologically meaningful targets necessitates robust integrative frameworks. In this context, artificial intelligence (AI) and machine learning methods offer powerful tools for data integration, target prioritization, and predictive modeling. In this Review, we summarize current insights into host factors that regulate influenza virus infection and discuss how multi-omics and AI-driven approaches are expediting host target discovery. Furthermore, we highlight the potential of these strategies to enhance antiviral development while addressing key challenges related to specificity, safety, and translational application. Collectively, these advancements lay a foundation that may support the rational design of next-generation host-directed antivirals. Full article

Poxviruses are large double-stranded DNA (dsDNA) viruses that cause important human and animal diseases, including smallpox and mpox. Poxviruses have also been identified in diverse bat populations; however, their potential for zoonotic transmission and adaptation to other mammalian hosts remains poorly understood. Poxviruses encode numerous immunomodulatory proteins that contribute to virulence, immune evasion, and host range. In this study, we performed a comparative genomic analysis of two bat-associated poxviruses belonging to the genus Vespertilionpoxvirus: hypsugopox virus (HYPV) and eptesipox virus (EPTV). Our analyses revealed 24 novel putative ORFs in HYPV and three in EPTV, thereby substantially expanding the inferred coding capacity of these viruses. Comparative analyses further revealed gene duplication and fragmentation events affecting several virulence and host range factors, as well as other unusual genomic features, including the presence of two divergent E3L homologs in EPTV. Together, our findings provide new insights into the genome evolution and potential host adaptation of bat-associated poxviruses and establish a foundation for future functional studies of Vespertilionpoxvirus biology, host–virus interactions, and zoonotic potential. Full article

The COVID-19 pandemic highlighted the urgent need to develop effective and broad-spectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log₁₀), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle. Full article

Crimean–Congo hemorrhagic fever virus (CCHFV) remains a major public health threat due to its high mortality rates and the absence of approved antiviral therapies. The viral ovarian tumor (OTU) protease is a critical virulence factor that suppresses host innate immunity through its deubiquitinase activity, making it an attractive therapeutic target. In this study, we employed a structure-guided approach to identify and validate novel small-molecule inhibitors targeting the non-catalytic Y89-W99 pocket of the OTU protease. Recombinant OTU protease was successfully expressed, purified, and refolded, yielding a soluble and enzymatically active protein. Cellular assays confirmed that the enzyme retains robust deubiquitinase activity, significantly reducing global ubiquitin conjugates in mammalian cells. In silico analysis of a putative DUB inhibitor library identified several candidate inhibitors with favorable binding interactions within the Y89-W99 pocket. Biochemical validation using a fluorometric Ub-AMC assay revealed that multiple small molecules strongly inhibit OTU activity, including OTUi-10 (~93% inhibition), OTUi-13 (~87%), OTUi-1 (~85%), OTUi-4 and OTUi-11 (~81%), and OTUi-9 (~76%). Additional moderate inhibitors included OTUi-12 (~67%), OTUi-19 and OTUi-21 (~66%), and OTUi-5 (~57%). In silico drug-likeness and toxicity profiling filtered the library to four fully compliant candidates, OTUi-4, OTUi-10, OTUi-11, and OTUi-12, all free of predicted toxicity alerts. These findings suggest that the Y89–W99 pocket may be a pharmacologically relevant site worthy of further investigation and identify OTUi-10, OTUi-4, and OTUi-11 as promising preliminary hit compounds. The results also provide initial insights that may guide future optimization and mechanistic studies of OTU protease inhibitors targeting CCHFV. Full article

Background: Viral attachment mediated by host cell surface receptors is the first step in viral infection. As a key cell surface receptor, heparan sulfate (HS) mediates the attachment and entry of numerous non-enveloped viruses in livestock, thereby serving as a crucial molecular target for studying virus–host interactions. Methods: Based on the structural scaffold of a nanobody (Nb; PDB: 7TJC), we rationally designed and constructed a mutant Nb targeting HS, designated HS-Mut-Nb1, using molecular docking, site-directed mutagenesis, molecular dynamics (MD) simulations, and experimental characterization. Results: Molecular docking indicated that the active site of wild-type Nb for HS binding was located within the cavity jointly formed by the complementarity-determining region 3 (CDR3) and the framework regions (FRs) of the wild-type Nb. A comprehensive analysis integrating virtual alanine scanning, site-directed mutagenesis, and MD simulations revealed that the combination of three point mutations (Phe47Arg, Asp99Tyr, and Tyr108Pro) significantly enhanced the binding affinity of Mut-Nb1 for HS, with a calculated binding free energy (ΔG) of −83.26 ± 3.06 kcal/mol. Enzyme-linked immunosorbent assay (ELISA) results further confirmed that Mut-Nb1 exhibited high affinity for HS (K_D = 65.87 nM) and specificity (positive/negative ratio, P/N = 3.84; cross-reactivity, CR < 6.60%). Conclusions: This study not only provides novel candidate molecules for elucidating the mechanism of HS–virus interactions and developing related inhibitors but also offers a reference for the rapid construction of mutant Nbs. Full article

Fibropapillomatosis (FP) is a disease that threatens the health and safety of sea turtles globally, with green sea turtles having the highest FP prevalence. FP is associated with Chelonid alphaherpesvirus 5, but the primary etiological agent remains unknown as expression and severity of the virus are influenced by host susceptibility, immunological status, development of epithelial lesions, and environmental factors. This review explores current understanding of FP in green sea turtles, focusing on etiology, pathological features, diagnostic approaches, and rehabilitation strategies. Emphasis is placed on the compounded nature of the disease, integrating factors that influence disease expression. Screening challenges are examined through the limitations of clinical, histological, and molecular methods, particularly in distinguishing latent from active infection. Rehabilitation practices, including surgical intervention and long-term supportive care, are evaluated in the context of treatment outcomes and recurrence risk. Collectively, the evidence supports the interpretation of FP as a disease shaped by host–pathogen–ecology interactions. Improved integration of diagnostic tools and greater focus on natural drivers are essential for advancing understanding of the disease and informing conservation and management efforts. Full article

Environmental stressors such as poor water quality, overstocking, and temperature spikes force shrimp to divert energy from growth and immunity to maintain homeostasis, increasing their susceptibility to opportunistic pathogens. Despite this risk, information on how these conditions affect viral and bacterial abundance, diversity, and community structure in shrimp farms remains scarce. To address this gap, this study offers a broad metagenomic analysis of the viral and bacterial communities in a shrimp farm, uncovering their diversity and ecological significance. In total, 13,572 viral operational taxonomic units (vOTUs) were recovered. Most viruses belonged to the realm Duplodnaviria, with Caudoviricetes dominating the libraries. Additionally, some contigs were linked to the Iridoviridae, a family that can affect fish and shrimp. Taken together, these findings highlight the critical role of virus–host interactions in marine environments and underscore the utility of metagenomic analysis for monitoring and safeguarding aquaculture health. Full article

The 9th National Congress of the Italian Society for Virology (SIV-ISV), entitled “One Virology—One Health”, took place in Turin at the Centro Congressi Lingotto from 22 to 24 June 2025. The meeting highlighted recent multidisciplinary and translational developments in virology, with a strong focus on the integration of the One Health perspective. Major themes included viral emergence and surveillance, genomic sequencing and bioinformatics, virus–host interactions, viral immunology and vaccines, structural and physical virology, environmental and food virology, zoonoses and animal infections, diagnostics and antiviral therapy, virus-based biotechnology and plant virology. The Congress aimed to: (i) bring together clinicians, basic researchers, veterinarians, environmental microbiologists, bioinformaticians, public-health professionals and industry to share methodologies and best practices; (ii) provide an interactive scientific environment promoting discussion and collaboration between senior investigators and trainees through plenaries, joint society sessions, invited talks, oral communications selected from abstracts, poster sessions, and mentoring panels; and (iii) identify priorities and inspire new research directions at the interface of human, animal and environmental health. More than 400 participants from national and international institutions attended the meeting, featuring distinguished plenary speakers, joint sessions with global networks, and numerous presentations of original unpublished data. This report summarizes the meeting’s scientific highlights, cross-disciplinary discussions, and proposed actions to strengthen One Health surveillance, computational infrastructures, and translational applications of viral biology. Full article

O’nyong-nyong virus (ONNV) is a mosquito-borne alphavirus responsible for large-scale epidemics in sub-Saharan Africa. As the closest evolutionary relative of Chikungunya virus (CHIKV), ONNV shares substantial genetic similarity and overlapping clinical manifestations with CHIKV. Mechanistic understanding of ONNV infection has therefore largely been extrapolated from CHIKV rather than directly established. However, ONNV exhibits distinct biological features, including predominant transmission by Anopheles mosquitoes and a clinical presentation characterized by prominent lymphadenopathy with limited acute joint edema. These distinctions underscore the need for an integrated synthesis of experimentally validated determinants of ONNV infection. In this review, we summarize current evidence on molecular and immunological factors regulating ONNV infection in mammalian hosts and mosquito vectors. We first discuss species-specific viral clearance, host dependency factors, intrinsic antiviral restriction mechanisms, protective innate immunity, inflammatory pathology, and mechanism-informed therapeutic strategies in mammalian hosts. We then examine stage-specific immune regulation in Anopheles mosquitoes, emphasizing mechanisms that constrain viral replication while permitting persistent infection and transmission. Finally, we discuss nsP3-dependent vector specificity and the potential contribution of alternative mosquito species to ONNV ecology. Together, this review provides an integrated framework for understanding how host factors, immune responses, and vector-specific adaptations shape ONNV infection, pathogenesis, and transmission. Full article