New nonacyclic duclauxin derivatives with potent anti-influenza activities from Antarctic fungus Penicillium sp. CPCC 401065.

Objective: To evaluate the antiviral effect, clinical efficacy, safety and tolerability of pixavir marboxil in adult patients with acute, uncomplicated influenza. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase Ⅱ clinical trial. Eligible participants were adults aged 18 to 64 years with acute, uncomplicated influenza, presenting within 48 hours of symptom onset with an axillary temperature ≥38.0 ℃ and ≥1 moderate-to-severe influenza symptom, who were neither severely ill nor at high risk for severe disease. Exclusion criteria included known hypersensitivity and recent antiviral use or vaccination. Participants were centrally randomized (1∶1∶1∶1) to oral pixavir marboxil (40 mg, 80 mg, or 40+40 mg) or placebo. Randomization was stratified by body weight (<80 kg vs.≥80 kg) and baseline influenza symptom score (<12 points vs.≥12 points). Rescue medications were permitted as clinically indicated during follow-up. The primary endpoint was the time to influenza virus RNA negativity by RT-PCR (time from first dose to the first RNA measurement below the lower limit of detection). Secondary endpoints included the time to relief of all influenza symptoms (severity scores of 0 or 1 for all 7 symptoms, sustained for ≥21.5 hours), time to cessation of infectious viral shedding by virus titer, time to resolution of fever, time to recovery to pre-influenza health status, changes from baseline in EQ-5D-5L scores, and the incidence of adverse events. Statistical analyses were performed using SAS 9.4. Efficacy was analyzed in the intention-to-treat infected (ITTI) and intention-to-treat (ITT) populations. Time-to-event data, including the primary endpoint, were estimated using the Kaplan-Meier method and compared between groups using the stratified Peto-Prentice generalized Wilcoxon test. Categorical data were analyzed using the Fisher's exact test or the Mantel-Haenszel test. Results: A total of 202 patients with influenza B were enrolled. In the ITTI population (107 cases), the median time to influenza virus RNA negativity was 28.2 h (95%CI: 19.73-43.88) in the 80 mg group, 35.5 h (95%CI: 23.43-45.05) in the 40 mg+40 mg group, and 42.4 h (95%CI: 22.60-57.53) in the 40 mg group, compared with 48.1 h (95%CI: 23.25-83.67) in the placebo group; between-group differences were not statistically significant (all P>0.05). The median times to cessation of infectious viral shedding by virus titer (TCID50) for the pixavir marboxil were [80 mg: 19.5 h (95%CI: 15.17-22.80); 40 mg: 22.6 h (95%CI: 14.72-44.85); 40 mg+40 mg: 23.1 h (95%CI: 18.63-26.98)] were versus the 45.8 h (95%CI: 20.20-68.57) in the placebo group; only the 80 mg group reached a statistically significant difference (P=0.027). In the ITT population (200 cases), pixavir marboxil 40 mg significantly shortened the median time to relief of all influenza symptoms compared to the placebo group [37.7 h (95%CI: 22.23-49.33) vs. 68.2 h (95%CI: 47.70-97.17), P=0.009], whereas the 80 mg group showed only a non-significant trend toward shortening 45.8 h [(95%CI: 34.50-62.67) vs. 68.2 h]. The median time to resolution of fever was significantly reduced in both the 40 mg [24.1 h (95%CI: 19.40-30.97)] and 80 mg [22.9 h (95%CI: 19.48-27.00)] groups compared with placebo [44.0 h (95%CI: 34.67-50.85)], with reductions of 19.9 h and 21.1 h, respectively (both P<0.001). The median time to recovery to pre-influenza health status was significantly shortened in the 80 mg [127.7 h (95%CI: 99.65-168.77)] and 40 mg [152.1 h (95%CI: 105.55-171.83)] groups compared with placebo [198.1 h (95%CI: 167.10-210.52)], with reductions of 70.4 h and 46.0 h, respectively (both P<0.05). The incidence of adverse events was comparable across groups: 13.5% (40 mg), 18.0% (80 mg), 20.4% (40 mg+40 mg), and 20.4% (placebo). No baseline or treatment-emergent resistance mutations were detected. Conclusion: Single-dose pixavir marboxil regimens demonstrated potential benefits in improving infectivity-related virologic measures and alleviating clinical symptoms in adults with uncomplicated influenza, with favorable overall tolerability. These findings provide a basis for subsequent confirmatory clinical trials.

RNA viruses are the most abundant group of pathogens on the planet; however, little is known about their association with amphipods (Crustacea: Peracarida). Here, we explore RNA virus diversity across invasive and native amphipod species inhabiting freshwater, marine, brackish and terrestrial environments around the globe, and analyse this data in relation to host invasion status, environment type, and between host taxa. We sampled tissue from 8 amphipod populations and screened an additional 152 from NCBI for RNA viruses. In total, 412 viral contigs were recovered, including 134 novel virus species, 41 with complete genomes. Viral contigs were associated with the: Articulavirales (n=35); Bunyavirales (n=38); Durnavirales (n=6); Ghabrivirales (n=28); Hepelivirales (n=43); Jingchuvirales (n=16); Martellivirales (n=4); Mononegavirales (n=139); Nidovirales (n=1); Nodamuvirales (n=2); Picornavirales (n=97); Wolframvirales (n=3). The alpha diversity of RNA viruses significantly differed between environments (freshwater, marine, and brackish) and amphipod host species. Host invasion status was not a significant driver in viral diversity. β diversity analysis revealed no significant difference in multivariate dispersion between environments, suggesting that freshwater, marine and terrestrial environments are equally rich in amphipod virus diversity; however, environment did have a significant effect on the viral community composition. This study contributes to our view of viral evolution and diversification among the Crustacea and boosts our understanding of RNA virus diversity and host range associated with invasion ecology and disease ecology within benthic communities.

Micropterus salmoides rhabdovirus G protein interacts with VDAC to trigger mitochondrial DNA/cGAS-STING pathway-mediated antiviral immune responses.

Genetic and pathogenic characterization of a Korean NADC30-like PRRSV strain associated with high fever and mortality.

Niemann-Pick C1 maintains cholesterol homeostasis in late endosomes to drive hepatitis B virus endosomal escape.

The turnip mosaic virus (TuMV) is an RNA virus that poses a significant threat to crops. The coat protein (CP) plays a crucial role in the viral life cycle, including mediating host infection and cell-to-cell movement, which makes it an ideal target for antiviral drug development. In this study, a series of structurally diverse synthetic indolylureas were screened against TuMV CP using high-throughput methods such as isothermal titration calorimetry (ITC) and microscale thermophoresis (MST). This led to the identification of compound SST21, which exhibits a high affinity for TuMV CP. Further experiments revealed that SST21 also binds to other homologous coat proteins from the Potyvirus genus, suggesting its potential as a broad-spectrum antiviral agent. Through molecular docking and point-mutation validation, the H183A residue in TuMV CP was identified as a key site for SST21 binding. In vivo experiments demonstrated that SST21 exhibits superior antiviral activity compared with ningnanmycin. Transmission electron microscopy observations indicated that SST21 disrupts the viral particle integrity. Additionally, omics analysis and defense enzyme activity assays showed that this compound was also found to modulate the plant immune responses. Together, these findings provide new insights into and experimental evidence for the development of novel plant antiviral strategies.

Research note: A novel double-gene deleted vaccine against hypervirulent MDV variant generated by CRISPR/Cas9-based gene editing.

Pheidole megacephala (Fabricius), the African big-headed ant, is one of the most significant invasive species and has become dominant in disturbed environments worldwide. Its presence poses serious threats to agriculture and biodiversity, highlighting the need for innovative and sustainable pest management strategies. One promising direction is the use of positive-sense single-stranded RNA (+ssRNA) viruses as biocontrol agents. This study investigates a novel control approach by integrating Pheidole megacephala virus 3 (PmV3), a member of Picornavirales, into alginate hydrogel as a viral delivery system for P. megacephala. Alginate hydrogel effectively served as a stable and environmentally friendly carrier, enabling controlled release of +ssRNA viruses over time. Despite replication occurring primarily in worker ants, PmV3 infections were detected in queens and brood by Day 17 after inoculation, indicating successful colony-level viral transmission. Reverse-transcription RT-PCR confirmed viral presence and tagged RT-PCR verified active replication within workers. Kaplan-Meier survival analyses showed significantly reduced worker ant survival in four of 10 treated colonies, demonstrating measurable pathogenic effects of the viral treatment. This study demonstrates the successful incorporation and delivery of +ssRNA viruses using alginate hydrogels and provides clear evidence of viral transmission, replication and colony-level impacts in P. megacephala. These findings highlight the potential of virus-loaded hydrogels as a promising, environmentally friendly tool for developing biologically based control strategies against invasive P. megacephala populations. © 2026 Society of Chemical Industry.

Impact of sensitivity difference between two widely used HDV RNA quantification assays on the management of HDV-infected patients treated with bulevirtide.

Alphaviruses, including significant human pathogens like Chikungunya (CHIKV), Venezuelan Equine Encephalitis (VEEV), and the model Sindbis virus (SINV), pose a considerable global health threat. Their ability to establish infection and cause disease is critically dependent on successfully subverting the host's innate immune defenses, particularly the Type I Interferon (IFN-I) system. This review provides a comparative analysis of the molecular strategies employed by CHIKV, VEEV, and SINV to dismantle these antiviral pathways. We first outline the conserved principles that form a core alphavirus "toolkit" for evasion, such as the formation of membrane-bound replication factories to shield viral RNA from cytosolic sensors and NSP1-mediated mRNA capping to mimic host transcripts. The review then delves into the divergent, virus-specific tactics, highlighting the central role of the non-structural protein 2 (NSP2) as a master antagonist. We contrast the aggressive strategies of pathogenic alphaviruses-such as CHIKV NSP2-mediated cleavage of MAVS and degradation of STAT2, and VEEV-induced degradation of STAT1-with the more subtle, modulatory approach of SINV, which relies more on a global shutdown of host gene expression. These distinct molecular mechanisms are directly correlated with their varying pathogenic outcomes. Furthermore, we examine the remarkable adaptability of these strategies between vertebrate hosts, where suppressing the IFN system is paramount, and invertebrate vectors, where evading the RNAi pathway is the primary challenge. A comprehensive understanding of these commonalities and divergences in immune evasion is essential for the rational design of broad-spectrum antiviral therapeutics and next-generation vaccines.

Porcine CD161 promotes Japanese encephalitis virus entry: a potential host-directed antiviral target.

Activation of host endogenous reverse transcriptase in response to white spot syndrome virus infection in Penaeus monodon.

Deciphering the core antiviral mechanism of Yinqiao powder: Inhibition of dengue virus adsorption mediated by wogonin via host receptor HSP90AA1 blockade.

Local immune responses in tick-bite skin during SFTSV infection are associated with type I interferon signaling and monocyte-lineage cell recruitment.

SARS-CoV-2 Delta, not Omicron, drives Transferrin receptor-1 upregulation, inflammatory activation, and viral persistence in macrophages.

A proximity induced strand displacement amplification and CRISPR/Cas12a-based SERS assay for ultrasensitive detection of dengue virus.

Antiviral potential of galactose-binding lectin from Vatairea macrocarpa seeds against SARS-CoV-2.

West Nile Virus inhibits type I interferon response via TRIM71 in human microglial cells.

Comparative analysis of next-generation sequencing methods for whole-genome sequencing of seasonal influenza viruses.