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Chinese rice-field eel rhabdovirus (CrERV), an emerging viral pathogen, causes massive death in rice-field eels (Monopterus albus), thus threatening the industry’s development. There is currently no established treatment strategy for CrERV. This study evaluated the anti-CrERV effects of schisandrin B (Sch B) in vitro and in vivo. The results indicated that Sch B at 20 mg/L could inhibit the expression of the CrERV G protein, with a maximum inhibition rate of 69.5%. Additionally, Sch B mitigated the nuclear damage and mitochondrial membrane potential decline induced by CrERV, thereby preserving cellular morphology. A time-of-addition study suggested that Sch B might exert its antiviral effects during the mid-stage of viral replication. In vivo, Sch B exhibited promising preventive and therapeutic effects against CrERV infection in rice-field eels, enhancing their survival rate by 57% and 51%, when added at 0.075% and 0.025%, respectively. Overall, the natural product Sch B was proven to have excellent anti-CrERV activity, with broad prospects for application in aquaculture.

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming—particularly involving lipid and sphingolipid metabolism—was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development.

Spring viremia of carp virus (SVCV) causes devastating losses in aquaculture. Coumarin has an advantageous structure for the design of novel antiviral agents with high affinity and specificity. In this study, we evaluated a hydroxycoumarin medicine, i.e., 7-(6-benzimidazole) coumarin (C10), regarding its anti-SVCV effects in vitro and in vivo. Results showed that up to 12.5 mg/L C10 significantly inhibited SVCV replication in the epithelioma papulosum cyprini (EPC) cell line, with a maximum inhibitory rate of >97%. Furthermore, C10 significantly reduced cell death and relieved cellular morphological damage in SVCV-infected cells. Decreased mitochondrial membrane potential (ATm) also suggested that C10 not only protected mitochondria, but also reduced apoptosis in SVCVinfected cells. For in vivo studies, intraperitoneal injection of C10 resulted in an anti-SVCV effect and substantially enhanced the survival rate of virusinfected zebrafish. Furthermore, C10 significantly enhanced antioxidant enzyme activities and decreased reactive oxygen species (ROS) to maintain antioxidant-oxidant balance within the host, thereby contributing to inhibition of SVCV replication. The up-regulation of six interferon (IFN)-related genes also demonstrated that C10 indirectly activated IFNs for the clearance of SVCV in zebrafish. This was beneficial for the continuous maintenance of antiviral effects because of the low viral loads in fish. Thus, C10 is suggested as a therapeutic agent with great potential against SVCV infection in aquaculture.

Background: Chandipura virus (CHPV) is an emerging rhabdovirus primarily affecting pediatric populations in India, causing acute encephalitis syndrome (AES) with high mortality rates. First identified in 1965, CHPV has resurfaced in several outbreaks, the most recent being in 2024, with significant public health implications. The virus is transmitted primarily by sandflies, particularly Phlebotomus spp., and has been associated with a rapid progression of symptoms, leading to severe neurological damage and death. Despite advances in diagnostic techniques, no specific antiviral treatment or licensed vaccine currently exists. Main Body of Abstract: This manuscript reviews the latest findings on CHPV, focusing on diagnostic advancements, treatment strategies, and public health responses. Reverse transcription–polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) have emerged as vital tools for rapid and accurate diagnosis, enabling the identification of CHPV in clinical and environmental samples. Antiviral therapies, such as ribavirin and favipiravir, have shown promise in vitro and preclinical models, but human trials are lacking. Additionally, the virus’s unique epidemiology, including its reliance on sandfly transmission, complicates control efforts, particularly in resource‐limited settings. The 2024 outbreak, with a case fatality ratio of over 30%, highlights the urgent need for improved surveillance, vector control measures, and public health interventions to curb the spread of CHPV. Conclusion: Despite considerable progress in diagnostics and experimental treatments, significant challenges remain in controlling CHPV outbreaks. The lack of specific antiviral therapies and vaccines continues to hinder effective management. Strengthened vector control strategies, advanced diagnostic infrastructure, and ongoing research into antiviral development are essential for mitigating the impact of CHPV in affected regions. International collaboration and sustained public health efforts will be crucial in preventing future outbreaks and reducing the disease burden.

Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre‐symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti‐lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11‐dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell‐dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ‐binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization‐independent T cell‐mediated effects, even against an established CNS infection by a lethal neurotropic virus. Synopsis Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication. Peripheral administration of mAb F11 reduces CNS viral replication and prevents mortality, following infection of mice with a lethal dose of either Australian bat lyssavirus (ABLV) or rabies virus (RABV). Therapeutic efficacy of F11, a human IgG1, requires a functional antibody Fc region, implicating the mechanistic involvement of immune cells bearing FcRγ. F11 efficacy requires an intact host adaptive immune response, particularly CD4 T cells. Administration of F11 alters both the proportions and phenotypes of immune cells in the brains of ABLV‐infected animals. Virus persists chronically at a low level in the brains of F11‐treated animals, but animals remain free of disease signs. Graphical Abstract Rabies is a fatal viral disease of humans, with uniform mortality once central nervous system (CNS) invasion occurs and symptoms appear. This study demonstrates that a single‐dose monoclonal (mAb) therapy can yield a functional cure for rabies, even after robust CNS replication.

RNA viruses exhibit high mutation rates, necessitating antivirals targeting conserved infection mechanisms. In this study, viral hemorrhagic septicemia virus (VHSV), a non-human pathogenic negative-sense RNA virus, was used as a surrogate model to enable high-throughput antiviral screening under reduced biosafety conditions. A recombinant VHSV expressing enhanced green fluorescent protein was used to screen 17,265 compounds, 2000 plant extracts, and 100 marine extracts. Among the candidates, the leaf extract of Phellodendron amurense Rupr. (PL extract) exhibited antiviral activity with low cytotoxicity (selectivity index ≈ 10). The extract reduced viral infectivity in a dose-dependent manner and showed cross-activity against snakehead rhabdovirus. Mechanistic analyses indicated that the PL extract acts primarily at early stages of infection. Virucidal assays demonstrated direct, time-dependent inactivation of viral particles, while pre-treatment reduced host cell susceptibility. Time-of-addition experiments confirmed that antiviral activity was restricted to early infection, suggesting interference with viral attachment or entry rather than intracellular replication. Fractionation revealed that activity was associated with the non-polar n-hexane fraction, implicating lipophilic compounds that may disrupt viral envelope integrity or membrane interactions. These findings suggest that P. amurense leaf extract is a promising candidate for broad-spectrum antivirals targeting conserved entry processes in enveloped RNA viruses.

The plaque assay has long served as the “gold standard” to measure virus infectivity and test antiviral drugs, but the assay is labor-intensive, lacks sensitivity, uses excessive reagents, and is hard to automate. Recent modification of the assay to exploit flow-enhanced virus spread with quantitative imaging has increased its sensitivity. Here we performed flow-enhanced infection assays in microscale channels, employing passive fluid pumping to inoculate cell monolayers with virus and drive infection spread. Our test of an antiviral drug (5-fluorouracil) against vesicular stomatitis virus infections of BHK cell monolayers yielded a two-fold improvement in sensitivity, relative to the standard assay based on plaque counting. The reduction in scale, simplified fluid handling, image-based quantification, and higher assay sensitivity will enable infection measurements for high-throughput drug screening, sero-conversion testing, and patient-specific diagnosis of viral infections.

The interferons (IFNs) are a large family of multifunctional secreted protein involved in antiviral defense, cell growth regulation, and immune activation. The human IFNs are used worldwide as antiviral drugs. Here, we present cDNAs encoding 13 novel feline IFN-ω (FeIFN-ω) subtypes that share 95%–99% amino acid sequence identity. FeIFN-ω2 and FeIFN-ω4 have seven additional amino acids at position 109 that are not present in other subtypes. Sequence identity of the present FeIFN proteins encoded by the 13 subtypes is approximately 57% compared with human IFN-ω (HuIFN-ω). All 13 FeIFN-ω subtypes were expressed in Escherichia coli using a periplasmic expression system. The antiviral activity of each product was evaluated in vitro. In addition, subtype FeIFN-ω2 was cytoplasm expressed in E. coli and secretion expressed in Pichia pastoris. The purified mature recombinant protein demonstrated significant antiviral activity on both homologous and heterologous animal cells in vitro.

Intranasal application of vesicular stomatitis virus (VSV) results in the initial infection of the olfactory receptor neurons and a rapid progression of the virus through the mouse central nervous system (CNS). Interleukin-18 (IL-18) is an 18.3-kd cytokine that induces interferon gamma (IFN-γ) production in mice. IL-18 is synthesized as an inactive precursor that is cleaved and activated by caspase-1/interleukin-1β converting enzyme (ICE). IL-18 shares several biological properties with IL-12, including the ability to induce IFN-γ production in T lymphocytes and natural killer (NK) cells. In the CNS, microglia and astrocytes produce IL-18 and IL-12. We have previously shown that IL-12 promotes recovery from VSV encephalitis. This led us to examine the potential role of IL-18 in the pathogenesis of VSV encephalitis. We show that both IL-18 and caspase-1 mRNA are consistently present in the CNS of mice. The addition of exogenous IL-18 to cell cultures does not affect the production of VSV, and addition of exogenous IL-18 at the time of infection does not alter the morbidity or mortality of BALB/c mice. In vitro studies with neutralizing monoclonal antibody to IL-18 had no effect. From these results we conclude that in this system and under the experimental conditions used, unlike IL-12 and IFN-γ, IL-18 does not play a significant role in the host response to VSV infection.

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.