Yezo virus (YEZV) is an emerging tick-borne orthonairovirus that causes febrile illness and hepatic injury in humans. However, its pathogenesis and effective antiviral interventions remain poorly characterized. In this study, we generated a lethal, mouse-adapted YEZV strain through 30 serial passages in C57BL/6 mice. The adapted strain successfully recapitulated key clinical and pathological features of human YEZV infection, including leukopenia, thrombocytopenia, and hepatitis, as evidenced by elevated serum transaminases, high hepatic viral loads, and histopathological necroinflammatory lesions. Notably, female mice exhibited significantly higher mortality than males, revealing a sex-associated difference in disease susceptibility. Antiviral evaluation demonstrated that both favipiravir and ribavirin significantly suppressed in vivo YEZV replication, improved survival, and reduced hepatic viral burden. Collectively, this model establishes a rigorously validated platform for mechanistic studies of YEZV pathogenesis and the preclinical evaluation of antiviral therapeutics.

Plant diseases continuously threaten crop yield and quality. Given the overuse of chemical agents, developing antiviral and fungicidal agents from natural products represents a promising sustainable strategy. In this study, a series of raspberry ketone derivatives were designed, synthesized, and evaluated for their antiviral and fungicidal activities. Most compounds exhibited better antiviral activity than ribavirin; in particular, compounds 3iand 5h-5j showed significantly higher antiviral activity (EC50: 144-199 μg/mL) than ningnanmycin (EC50: 235 μg/mL) and thus emerged as novel antiviral candidates. Compound 3i was chosen for antiviral action mechanism research, which revealed that it can cause 20S coat protein (CP) polymerization, thereby affecting the assembly of TMV particles. The results of molecular docking and DFT calculations further provided a molecular basis for the observed antiviral activity. Additionally, these compounds displayed broad-spectrum fungicidal activity against six plant pathogens and met pesticide-likeness criteria in ADME predictions. This research advances the development of raspberry ketone derivatives as green pesticides.

Viral respiratory infections still exist as a major global health concern. Influenza A viruses and human metapneumoviruses are among the main pathogens responsible for infections that can progress to severe acute respiratory forms. Despite the availability of certain therapeutic options, the need for effective treatment remains an issue. The exploration of innovative approaches based on medicinal plants, capable of simultaneously targeting several viruses, represents a promising strategic option for limiting the viral activity of these pathogens. In this work, an integrated computational workflow combining molecular docking, ADMET prediction, molecular dynamics (MD) simulations, and MM-PBSA binding free-energy analysis was applied to evaluate previously reported antiviral phytoconstituents for their broad-spectrum antiviral potential by simultaneously targeting influenza A virus neuraminidase (NA) (PDB ID: 2HT7) and the human metapneumovirus (HMPV) fusion protein (F) (PDB ID: 7SEJ). Molecular docking analyses identified 37 phytoconstituents with favorable multi-target binding affinities toward both NA and F proteins, exhibiting more favorable predicted binding energies than the reference compounds oseltamivir and ribavirin. In addition, ADMET prediction, including bioavailability assessment and analysis of pharmacokinetic and toxicological properties, identified several compounds with favorable profiles, notably compounds E10, M294, M329, C11, C5, and M274. MD simulations followed by MM-PBSA binding free-energy calculations further validated the stability and binding behavior of the highest-ranked protein-ligand complexes identified through the sequential screening workflow. Overall, compounds M294 and C11 emerged as the most promising broad-spectrum antiviral lead candidates against both influenza A NA and HMPV F protein. Nevertheless, these findings are based on computational predictions and require confirmation through in vitro antiviral assays followed by in vivo studies.

Repurposing of approved drugs offers a rapid and cost-effective strategy for the identification of new therapeutic applications, particularly for difficult-to-treat and therapy-resistant cancers. Ribavirin, which is a synthetic guanosine analog and used as an antiviral drug, has demonstrated promising anticancer activity. To that end, the literature has presented varied anticancer mechanisms of action for ribavirin. This review integrates the current mechanistic evidence and proposes a working hypothesis in which ribavirin may influence interconnected metabolic, signaling, and translational processes that collectively induce its anticancer activity. Ribavirin inhibits inosine monophosphate dehydrogenase and depletes GTP, which may influence small GTPase-dependent signaling such as Ras-driven pathways. More recently, modulation of metabolic signaling by ribavirin has been proposed through the inhibition of AMP-activated protein kinase-associated pathways. These upstream perturbations may propagate through oncogenic signaling networks and complement the suppression of eukaryotic translation initiation factor 4E-dependent mRNA export and protein synthesis. Further, ribavirin treatment indirectly influences epigenetic regulators, inflammatory mediators, and immune checkpoint pathways, contributing to broader reprogramming of tumor cell behavior. Ultimately, ribavirin's effects lead to cell cycle arrest, apoptosis, and enhanced chemosensitivity across diverse cancer types. Taken together, the available evidence supports the hypothesis that ribavirin may function as a multilevel modulator of cellular growth networks, although the mechanistic relationships among these pathways remain incompletely defined. SIGNIFICANCE STATEMENT: This review theorizes ribavirin as a systems-level anticancer agent by integrating its effects on guanine nucleotide metabolism, oncogenic signaling, and eukaryotic translation initiation factor 4E-dependent translation into a unified metabolic-signaling-translation axis. In addition, it identifies the disparities in the mechanistic literature, which may assist in designing future studies.

This Correspondence responds to Oh and colleagues' study on nosocomial respiratory virus infections in hematologic malignancies and risk factors for progression to lower respiratory tract infection. We raise three methodological concerns: (1) the landmark analysis used to evaluate URTI-stage ribavirin therapy excludes patients who progressed or died before landmark time points, introducing selection bias by conditioning on a collider; (2) antiviral therapy analyses are severely underpowered (only 15 PIV and 9 RSV treated patients), with wide confidence intervals precluding definitive conclusions and substantial Type II error risk; and (3) combining glucocorticoid exposures from different indications (short-course pulse vs. prolonged therapy) may mask heterogeneous effects on immune function and viral progression. We commend the authors' risk stratification framework while urging cautious interpretation of antiviral efficacy data and recommending future prospective studies with adequate sample sizes and refined corticosteroid characterization.

Despite the availability of a safe and effective measles vaccine for several decades, measles remains a significant cause of morbidity and mortality worldwide, causing 95,000 deaths in 2024 alone. Currently, there is no licensed therapeutic agent against measles, and treatment is only supportive. This is a review of articles published from 2015 to 3 June 2025, on therapeutic agents used or under investigation against measles. Ribavirin has been used in severe measles cases; nevertheless, there are no randomized clinical trials so far. New delivery systems, such as polymer-based formulations and nanoparticles, have markedly increased ribavirin's efficacy, while cytotoxicity remained low. Viral membrane fusion (F) protein inhibitors and viral RNA polymerase inhibitors are promising next-generation therapeutics against measles and have been tested in animal models with good results. Lastly, interferons (IFNs) are key mediators of the innate immune response against measles, particularly for controlling brain infection. There are few reports indicating that repeated remdesivir courses, as well as intraventricular or intrathecal ribavirin or IFN, may temporarily stabilize the neurologic status of patients with subacute sclerosing panencephalitis. Intracranial administration of protein F inhibitors also demonstrated promising results in mice. Although several antiviral agents and natural products exhibit in vitro efficacy against measles virus, further research is required to determine their safety, pharmacological properties, and clinical efficacy before they can be considered therapeutic options. Overall, the development of antiviral agents against measles has been extremely slow. Therapeutic agents against measles are urgently needed.

Hepatitis E virus (HEV) infection, once regarded as a self-limiting hepatic disease confined to endemic regions, is now recognized as a systemic condition with a broad spectrum of extrahepatic manifestations. Among these, neurological complications-including peripheral neuropathies such as Guillain-Barré syndrome and neuralgic amyotrophy, and central nervous system involvement such as meningitis, encephalitis, and meningoencephalitis-are the most clinically relevant. Meningoencephalitis, though less common, is the most severe and underdiagnosed neurological expression of HEV infection. This narrative review examines current evidence on HEV-associated meningoencephalitis, covering epidemiology, pathogenesis, clinical features, and therapeutic strategies. Neurological disease is dominated by genotype 3 and frequently anicteric, with symptoms preceding or masking hepatic involvement. Pathogenesis is multifactorial, combining direct viral neurotropism-supported by HEV RNA detection in cerebrospinal fluid and replication in induced pluripotent stem cell (iPSC)-derived neurons and brain organoids-with immune-mediated mechanisms such as molecular mimicry and microglia-driven neuroinflammation. Diagnosis is often delayed by the absence of jaundice and low clinical suspicion, even though HEV remains an unrecognized cause in many unexplained encephalitis cases in high-income settings. Ribavirin remains the antiviral mainstay, but viral persistence within CNS sanctuary sites raises concerns about treatment adequacy and relapse; emerging antiviral and immunomodulatory strategies remain under investigation. HEV should be systematically considered in the diagnostic workup of unexplained neurological syndromes, regardless of overt hepatitis; heightened clinical awareness remains the most immediately actionable step toward reducing the burden of this still under-recognized condition.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are clinically relevant pathogens in lung transplant (LT) recipients, but their impact on lung function and the benefit of ribavirin remains uncertain. We conducted a prospective multicenter observational cohort study of adult LT recipients with RSV or hMPV infection diagnosed between 2021 and 2024 at five centers, with follow-up for up to 12 months. Ribavirin was prescribed at the treating physician's discretion. Multivariable analysis assessed the association between ribavirin and percentage change in forced expiratory volume in the first second (FEV1) at 90 days, using FEV1 three months before infection as baseline and adjusting for baseline FEV1, pre-existing chronic lung allograft dysfunction, and time since transplantation. Seventy-six patients were included; 60 (78.9%) had RSV and 16 (21.1%) hMPV. Lower respiratory tract infection occurred in 48.7%, and an acute ≥10% FEV1 decline at 14 days was observed in 29.3%. Among patients with lower respiratory tract infection, 45.9% received corticosteroids alone and 37.8% corticosteroids plus ribavirin. No statistically significant between-group differences in allograft dysfunction or mortality were observed. RSV and hMPV infections after LT were frequently associated with lower respiratory involvement and lung function decline. In this observational cohort, ribavirin use was not independently associated with 90-day FEV1 change; however, residual confounding and limited statistical power preclude conclusions regarding treatment efficacy.

The World Health Organization targets hepatitis C virus (HCV) elimination as a public-health threat by 2030. Phetchabun province, in lower northern Thailand, has historically reported one of the country's highest HCV seroprevalence rates. We describe a province-wide, decentralized test-to-treat micro-elimination program implemented within Thailand's universal health-coverage system. Adults aged 35-64 years (2020-2024) and individuals born before 1992 (late 2023) across all 11 districts were screened using fingerstick anti-HCV rapid diagnostic tests at sub-district health-promoting hospitals. Reactive participants underwent confirmatory HCV-RNA testing at three regional nodes. Eligible patients received pangenotypic sofosbuvir/velpatasvir for 12 weeks, with ribavirin added for cirrhosis. Sustained virological response at 12 weeks post-treatment (SVR12) was the primary outcome. Of 400,567 targeted individuals, 389,547 (97.3%) were screened; 18,340 (4.71%) were anti-HCV reactive. Confirmatory HCV-RNA testing was completed in 14,845 (80.9%), of whom 10,996 (74.1%) had active infection. Of 8961 treatment-eligible patients, 8842 (98.7%) received DAA therapy. Among 6719 evaluable for SVR12, 6474 (96.4%) achieved cure. This simplified, domestically financed, decentralized test-to-treat model achieved WHO-target-level diagnosis, treatment, and cure rates at provincial scale, offering a scalable framework for HCV micro-elimination in low- and middle-income countries.

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed viral haemorrhagic fever with expanding geographic range. As new regions encounter the disease, clinicians must make high-stakes decisions despite limited standardised management frameworks.

Two rearranged ent-clerodanes, Crotonvigas A-B (1-2), eight other diterpenoids, Crotonvigas C-J (3-10), four previously undescribed sesquiterpenes, Crotonvigas KN (11-14), together with fourteen known terpenoids were isolated from Croton laevigatus Vahl. Among them, compound 1 is a chlorinated rearranged ent-clerodane. Its absolute configuration was unequivocally established by single-crystal X-ray diffraction. The anti-DENV activity results revealed compounds 5 and 24 inhibited DENV-prM protein expression stronger than ribavirin (RBV) exhibiting a potential anti-DENV activity, with the half-maximal effective concentration (EC50) values of 14.04 μM and 9.27 μM, the half-maximal cytotoxic concentration (CC50) values of 93.53 μM and 80.34 μM, and selectivity index (SI) values of 6.66 and 8.67, respectively. The anti-ZIKV activity revealed that compound 22 dose-dependently suppressed ZIKV E protein, with the EC50 value of 21.13 ± 1.58 μM, the CC50 value of >200 μM, and SI value of >9.47.

Three rearranged jatrophane diterpenoids, eupheilosnoids A-C (1-3), were isolated from Euphorbia helioscopia. Compound 1 possesses a fused 5/6/6/4 tetracyclic carbon skeleton, whereas compounds 2 and 3 feature a 5/6/6/5 ring system. Compounds 1-3 were evaluated for anti-ZIKV activity. Among them, compound 2 exhibited potent anti-ZIKV activity with an EC50 of 2.09 μM, which was significantly superior to that of the positive control ribavirin (RBV). Further studies revealed that compound 2 significantly inhibited the expression of ZIKV envelope protein (ZIKV-E).

Functionalized imine-linked covalent organic polymers (COPs) have attracted tremendous attention as adsorbent. At present, most imine-linked COPs are functionalized relying on benzene groups, limiting sufficient flexibility for grafting diverse functional groups. Herein, Ugi reaction is employed to flexibly anchor carboxylic acids and isonitriles with diverse molecular structures onto the imine bonds of COP skeletons. Considering that four illegal food additives, salbutamol, ractopamine, terbutaline and ribavirin, can specifically bind with boric acid, this work selects 4-carboxyphenylboronic acid and tert‑butyl isocyanate, yielding a boronate affinity imine-linked COP. The adsorption performance of the obtained adsorbent is investigated in detail. The as-prepared adsorbent exhibits excellent selectivity, and high adsorption capacities ranging from 119.6 to 385.3 μmol/g towards four analytes. Moreover, the developed dispersive solid-phase extraction (DSPE) combined with HPLC gives low limits of detection (0.21-0.38 μg/kg) and wide linear ranges (1.2-300.0 μg/kg) for the four targets in feed samples. These results confirm the excellent adsorption properties of the adsorbent and verify the feasibility of Ugi reaction for post-synthetic functionalization of COPs.