Archives of Virology最新文献

SARS-CoV-2 utilizes the cell surface receptor angiotensin-converting enzyme 2 (ACE2) for entry and infection in the host cell. Thus, the molecular interface of the receptor binding domain (RBD) and ACE2 is a potential clinical target for SARS-CoV-2 infection. A small molecule inhibitor of ACE2 could block the entry of SARS-CoV‐2 and its emerging variants. This study characterizes the RBD-ACE2 interaction inhibition activity and antiviral activity of GR 127935. The binding affinity of GR 127935 to ACE2 was confirmed using Surface Plasmon Resonance (SPR). The compound inhibited RBD-ACE2 interaction in the ELISA assay (IC₅₀ = ~ 17 µM) and effectively blocked the entry of SARS-CoV-2 pseudovirus into HEK293T-ACE2-TMPRSS2 (IC₅₀ = ~ 1.2 µM). Further, the anti-SARS-CoV-2 activity of GR 127935 was evaluated in vitro using the Vero cell line and a SARS-CoV-2 clinical isolate. The most prominent inhibition (EC₅₀ = ~ 1.6 µM) was observed when the compound was added during the virus entry step. Finally, the GR 127935 treatment of BALB/c mice infected with the mouse-adapted strain of SARS-CoV-2 resulted in decreased viral load in the lungs along with a lower histopathology score. In summary, the GR 127935 molecule binds to ACE2, inhibits the molecular interaction between RBD and ACE2, and is effective in inhibiting virus replication. Thus, it is a promising potential therapeutic compound for treating human SARS-CoV-2 infections.

Pectobacterium brasiliense (Pbr) is known to be one of the most virulent Pectobacterium species and is generally widely distributed across the globe, especially known for causing soft rot in potato-tubers and black leg in potato-plants. Currently no treatment mechanism exists, and many studies have focused on alternative treatment approaches such as biocontrol agents. Several studies have used phages targeting Pectobacterium species as effective biocontrol agents. This study is the first description of a single-stranded DNA phage belonging to the family Microviridae that targets Pectobacterium. The novel Pectobacterium phage Mimer is proposed to belong to a new genus within the subfamily Bullavirinae in the family Microviridae. Phage Mimer has a genome size of 5879 nt with twelve predicted gene products. Seven out of twelve gene products could be assigned with a function based on either amino acid sequence or structural similarity. Gene synteny and phylogenetic analyses suggest that phage Mimer is part of the subfamily Bullavirinae. Phage Mimer proved to infect a broad range of Pbr isolates but showed a poor adsorption rate as only 17% of phage particles adsorbed within 10 min on the isolation host. Growth kinetics showed phage Mimer to have a latent period of 65 min and an average burst size of approximately 79 virions per cell. Phage Mimer is the first ssDNA phage targeting Pectobacterium and could be a promising biocontrol agent with great therapeutic potential, based on both the small genome size and the well-known genome architecture of model phage phiX174.

Enteroviruses, which belong to the Picornaviridae family, are implicated in a variety of illnesses that range from mild to severe, with some infections potentially being life-threatening. Among these, Enterovirus 71 (EV71) is recognized as one of the most virulent members of the enterovirus genus. Currently, there are no effective treatments available for EV infections. Ionophore antibiotics are small, hydrophobic, and lipophilic molecules approved for use in veterinary medicine as anti-coccidial feed additives. Notably, ionophore antibiotics such as monensin (MON) and salinomycin (SAL) have shown antiviral activity against specific virus groups, although the modes of actions are not yet well understood. This study investigates the antiviral effects and mechanisms of MON and SAL against enteroviruses. Our findings reveal a dose-dependent reduction in EV71 infection, with 50% inhibitory concentrations of 0.25 μM for MON and 1.49 μM for SAL. Mechanistic investigations demonstrated that both agents primarily inhibit EV71 infection at the entry stage, independent of viral binding and internalization. Furthermore, these agents effectively neutralized low pH levels within endolysosomes, which was associated with a decrease in antiviral efficacy when acidic conditions were maintained in the medium. Additionally, both agents showed the ability to block viral maturation, which requires an acidic environment. The antiviral effects of MON and SAL were also observed against various serotypes of enteroviruses. In summary, MON and SAL exhibit antiviral efficacy by neutralizing endolysosomal pH during the viral entry process, suggesting a potential broad-spectrum antiviral strategy that could be applicable to other viruses with similar replication pathways.

Subtype H8 avian influenza viruses (AIVs) are rarely reported and poorly characterized. We isolated nine H8Nx AIVs from wild birds in South Korea during 2019–2024. Whole-genome and phylogenetic analyses showed close relationships with Asian AIVs and frequent reassortment with other low pathogenic avian influenza viruses (LPAIVs). Time-scaled analysis indicated recent introductions of North American lineage viruses into South Korea, despite long-term independent evolution of Eurasian and North American lineages. Amino acid substitutions linked to mammalian adaptation were also found. These findings provide baseline data for continued H8 AIV surveillance in wild birds.

Grass carp reovirus is a major aquaculture biosecurity threat, causing acute outbreaks and diagnostic delays in hemorrhagic disease. For early warning of GCRV-II in aquaculture water, this study established a method using iron flocculation to concentrate viruses, with qPCR-based tracking and viral load quantification. Results show the S7 gene serves as a highly sensitive and stable monitoring marker, suitable for efficient water surveillance. Furthermore, viral load in aquaculture water negatively correlated with fish survival and pathology, validating environmental monitoring as an effective early-warning system for disease outbreaks. This provides an efficient molecular marker for GCRV-II monitoring and control.

Fibronectin is a high molecular weight glycoprotein critical to numerous physiological and pathological processes, including extracellular matrix organization, wound healing, immune responses, and interactions with pathogens. Evidence from various viral systems, including dengue, influenza, hepatitis B, and HIV-1, indicates that targeting fibronectin or disrupting its interactions can notably affect outcomes of viral infections in vitro. Alterations in the expression of fibronectin are associated with immune evasion mechanisms, including the inhibition of interferon signaling, thereby enabling viruses to survive and replicate with greater efficacy. In this review, we discuss how viruses can interact with fibronectin through arginyl-glycyl-aspartic acid motif (RGD) mimicry or other mechanisms. Finally, we explore the role of fibronectin in modulating host immune responses and its potential as a therapeutic target.

Coxsackievirus A10 (CV-A10) has become an important cause of hand, foot, and mouth disease (HFMD). Molecular surveillance in northern Vietnam during 2018–2020 revealed the introduction and rapid dominance of the genotype C lineage (CHN), replacing the previously endemic lineage (VNM). This shift was associated with a significant increase in detection and altered clinical severity, predominantly grade 2A (83.8%). Phylogenetic analysis revealed the close relatedness between the emerging Vietnamese strains and those circulating in China (2017–2024). These findings suggest lineage-dependent virulence in CV-A10, highlighting the need for lineage-level molecular surveillance to guide HFMD control and vaccine development.

The rise of multidrug-resistant Elizabethkingia anophelis (E. anophelis) presents a significant public health challenge. Here, we report the isolation, morphological and biological characterization, and genomic analysis of a novel lytic bacteriophage, XANYB1, targeting E. anophelis. XANYB1 was isolated from hospital wastewater in Xi’an, China, using a clinical strain as the host. Transmission electron microscopy revealed that XANYB1 belongs to the order Caudoviricetes, featuring icosahedral heads and long, non-contractile tails. Whole-genome sequencing showed very low similarity to known phages, confirming XANYB1 as a novel bacteriophage. The optimal multiplicity of infection (MOI) was determined, and one-step growth curve analysis indicated a latent period of 30 min and a lysis period of approximately 40 min. XANYB1 remained stable across a broad pH range (3–11), at temperatures up to 50 °C, and in the presence of up to 5% chloroform. Host range analysis showed that XANYB1 lysed 5 of 14 clinical E. anophelis isolates. In a mouse sepsis model, XANYB1 exhibited effective in vivo antimicrobial activity, highlighting its potential as a therapeutic candidate. These findings support the application of XANYB1 in phage therapy against multidrug-resistant E. anophelis infections.

Cachexia, a multifaceted wasting syndrome, profoundly impacts quality of life and survival rates in cancer patients. Gut inflammation is identified as a key player among the contributing factors for its development. Consequently, numerous studies have sought to characterize changes in gut microbiota of cachectic individuals, given the well-established roles of the gut microbiota in controlling and/or triggering both local and systemic inflammation in their hosts. Most of these investigations have applied mouse models of tumor-induced cachexia to show correlations between alterations in bacterial and fungal abundance in the digestive tract and the onset of cancer cachexia (CC). However, the role of viral dysbiosis in CC development remains unexplored. The present study aims to address this gap by characterizing the gut virome during the progression of murine cancer cachexia. Although our approach was limited to DNA viruses, our findings reveal that cachectic animals with Lewis lung carcinoma exhibited a subtle yet statistically significant modulation in composition (R² = 0.17622; p = 0.05). A linear discriminant analysis effect size (LEfSe) analysis revealed that the dysbiosis observed in the gut virome of CC animals was mostly characterized by a significant enrichment in giant viruses of the family Phycodnaviridae (LDA score, 4.2582; p-value, 0.004; pwr_app, 0.9984) and significantly decreased populations of bacteriophages of the families Microviridae (LDA score, 4.3458; p-value, 0.0127; pwr_app, 0.9065) and Inoviridae (LDA score, 3.3028; p-value, 0.0017; pwr_app, 0.9992). This cachexia-associated viral dysbiosis shares similarities with virome alterations documented in other conditions linked to gut inflammation, including, ulcerative colitis, Crohn’s disease, and Clostridioides difficile infection. These new insights suggest the potential contributions of viral communities to the pathophysiology of CC and other inflammation-driven diseases.

The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species. This review explores the molecular mechanisms underpinning this cross-species transmission, focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors, functions as a novel biological crucible for viral adaptation. Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations—such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans, potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity and that single HA mutations are sufficient to shift binding preference to human receptors. The unprecedented mammalian spread of clade 2.3.4.4b, coupled with its capacity for reassortment and the recent case of a dairy farm worker infection, underscores an urgent zoonotic and pandemic threat. This review contextualizes the outbreak within the fundamental principles of influenza virus receptor biology and viral evolution, highlighting critical knowledge gaps that must be addressed through integrated surveillance and multidisciplinary research. Understanding the interplay between host receptor distribution and viral plasticity in this new niche is paramount for mitigating the risk of a future influenza virus pandemic emerging from the bovine reservoir.