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At least 19 recordsLinked to original sources

PubMed2027

Screening of Antiviral Agents Against CHIKV Using Reporter Virus.

Chikungunya virus (CHIKV) causes a disease characterized by chronic musculoskeletal inflammation for which specific antivirals are not yet available. Currently, a supportive therapy to alleviate fever and pain is used, but it does not limit viral replication or the persistence of chronic arthritis symptoms. Thus, the identification and development of new active molecules against CHIKV is urgently needed. Here, we present a cell-based methodology that enables the implementation of a rapid and cost-effective strategy for high- and medium-throughput screening (HTS) of compounds, including repurposed drugs or novel molecules. This methodology allows for the identification of novel antiviral hits with a good activity and selectivity profile against CHIKV.

Antiviral Agents↗

PubMed2025

Antiviral Activity of the MEK1/2 Inhibitor Trametinib Against Lymphocytic Choriomeningitis Virus.

The lymphocytic choriomeningitis virus (LCMV) is a widespread pathogen that causes mild-to-severe infections to severe outcomes. In this study, we explored the potential of trametinib, a mitogen-activated protein kinase (MAPK) inhibitor, as an antiviral agent against LCMV. Trametinib demonstrated significant antiviral activity against two distinct LCMV strains, Armstrong and Cl13, with promising half-maximal inhibitory concentrations (IC50) and selectivity indices (SI) indicating its potency and safety profile. Mechanistic investigations revealed that trametinib interfered with multiple stages of the LCMV life cycle, including membrane fusion and genomic replication, leading to the robust inhibition of viral proliferation. Furthermore, trametinib disrupted the MEK/ERK signaling pathway, which is crucial for LCMV infection. In both in vitro and in vivo experiments, trametinib effectively reduced viral loads and mitigated pathological damage to the spleen and liver tissues. Overall, our findings suggest that trametinib is a promising novel therapeutic option for combating LCMV infection by targeting key stages of the viral life cycle and disrupting host cellular signaling pathways. Further exploration of the antiviral properties of trametinib is likely to pave the way for its clinical development as a treatment for LCMV infections.

Pyridones↗

PubMed2026

Bergamottin, a bioactive component of bergamot: dual inhibition of Japanese encephalitis virus internalization and genome replication.

Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.

Animals↗

PubMed2026

Insights into the Life Cycle and Therapeutic Agents for Monkeypox Virus Infection.

Since the first confirmed case in 1970, the monkeypox virus (MPXV) has emerged as a significant threat to global public health. The World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) on two occasions. Despite decades of research, only tecovirimat has been approved by the European Medicines Agency (EMA) for the treatment of MPXV infection. The genome and structure are similar between MPXV and other orthopoxviruses (OPXVs), suggesting that the strategies used for other OPXVs may be applicable to MPXV. This review systematically summarizes the genome, structure, and critical stages in the life cycle of OPXVs, especially MPXV. A variety of antiviral agents against MPXV and other OPXVs are discussed according to their distinct mechanisms of action: 1) blocking viral entry and fusion, 2) inhibiting DNA replication and processing, 3) disrupting transcription and mRNA processing, 4) preventing virion assembly, maturation and release, 5) modulating immune responses, and 6) mechanism unknown. Overall, this article provides a systematic review of current research progress on potential therapeutic targets and agent for MPXV, aiming to offer innovative insights and strategies for the development of effective therapeutic agents against mpox.

Animals↗

PubMed2026

Quercetin, a flavonoid, suppresses viral proliferation by interfering with the ubiquitin transfer from E1 to E2 enzymes.

Quercetin is recognized for diverse pharmacological activities. However, the mechanism underlying its broad-antiviral effects has not been elucidated. Herein, we identified quercetin as a potent inhibitor of both double-stranded DNA virus Bombyx mori nucleopolyhedrovirus (BmNPV) and single-stranded RNA virus porcine reproductive and respiratory syndrome virus (PRRSV). Surface plasmon resonance (SPR) revealed that quercetin targets host ubiquitin-activating enzyme 1 (Uba1) homologs. Uba1 knockdown reduced viral proliferation and enhanced the antiviral effect of quercetin, whereas Uba1 overexpression functioned oppositely. Quercetin bound Uba1 homologs with high affinity. Notably, mutation of two binding residues, Q977 and G978, significantly disrupted the binding between BmUba1 and quercetin, and abolished quercetin's antiviral activity. Quercetin obstructed the transfer of ubiquitin from Uba1 to the E2 enzyme Ubc6, impairing the ubiquitination process. Similarly, quercetin inhibited PRRSV proliferation via targeting Uba1 in mammals. These findings elucidate the molecular mechanism underlying the pharmacological effects of quercetin, providing a theoretical basis for the development of novel antiviral agents against both DNA and RNA viruses.

Quercetin↗

PubMed2025

Conserved Filovirus Proteins as Targets of Broad-Spectrum Antivirals.

Filoviruses are enveloped, non-segmented, negative-strand RNA viruses belonging to the Filoviridae family, which includes five genera: Ebolavirus, Marburgvirus, Cuevavirus, Striavirus, and Thamnovirus. Members of this family cause severe and, often, fatal hemorrhagic fevers in humans and non-human primates, with high mortality rates. To date, only two filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are known to infect humans and are listed as priority pathogens by the World Health Organization due to their potential for re-emergence and the current lack of effective vaccines and antiviral treatments. In this study, we identify and characterize conserved binding sites within key filoviral proteins to support the development of broad-spectrum, direct-acting antiviral agents. We validated the significance of these conserved regions for drug discovery using existing experimental data. Our analysis revealed notably high sequence similarity among proteins from filoviruses capable of infecting humans (EBOV, TAFV, BDBV, SUDV, MARV, and RAVV) compared to those from non-zoonotic species, with the highest conservation observed in the L and VP40 proteins-both critical for viral genome transcription and replication. Furthermore, we compiled and analyzed available experimental data on known antiviral compounds targeting these proteins, identifying several agents with cross-filovirus activity, including Galidesivir, Remdesivir, and Favipiravir. The integrated approach described here-combining sequence and structural conservation analysis with chemical structure and antiviral activity data-demonstrates a strategy that could be extended to the development of broad-spectrum therapeutics across multiple viral families.

Broad Spectrum Antiviral↗

PubMed2025

Dynamic Interplay Between miR-133a and RBMX During Dengue Virus Infection.

Viruses are obligate intracellular pathogens with limited genome capacity, relying entirely on host factors and cellular machinery for sustainable infection. In the present study, we demonstrate that dengue infection modulates the expression of RBMX (an RNA-binding protein) and miR-133a. Viral infection elevates the expression of the RBMX gene while downregulates the level of miR-133a. Additionally, Targetscan tool analysis shows that miR-133a possesses a potential binding site in the 3'UTR region of the RBMX gene, and our luciferase data indicate the miR-133a-mediated regulation of RBMX expression. Intriguingly, our time point study in Huh7 cells overexpressing the synthetic form of miR-133a mimic and inhibitor indicates the convoluted interaction between miR-133a and RBMX regulation during DENV infection. After 24 h postinfection (hpi), miR-133a significantly suppresses both the RBMX expression and viral RNA levels, acting as an antiviral agent by targeting the expression of the RBMX gene. Additionally, our immunoprecipitation result suggested the central role of DENV 3'UTR in regulating the expression of both RBMX and miR-133a. Furthermore, our study on RBMX Overexpression illuminates the vital function of RBMX protein in the DENV life cycle. Overexpression of the RBMX gene in ivermectin-pretreated cells partially rescues viral replication. This comprehensive study explicates the dynamic miRNA/RBPs regulatory axis during DENV pathogenesis.

MicroRNAs↗

PubMed2026

Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.

Interferon resistance has been implicated in SARS-CoV-2 escape from innate immunity, but exogenous interferon's impact on viral evolution and diversity is unknown. SNG001, an inhaled interferon-β1a treatment, was evaluated in the ACTIV-2/A5401 randomized controlled trial of therapeutics for COVID-19. We measured viral kinetics and performed whole-genome sequencing on longitudinal nasal swabs collected from ACTIV-2 participants who received either SNG001 or placebo to assess viral sequence diversity. No difference in nasal viral load decay was detected between study arms when stratifying by SARS-CoV-2 variant or by viral culture conversion. Compared to placebo participants, the SNG001-treated participants displayed significantly lower nonsynonymous amino acid average pairwise distance, indicating lower sequence diversity. Similarly, SNG001-treated individuals also developed numerically fewer nonsynonymous mutations during their infection in ORF1a, ORF1b, Spike, and Nucleocapsid. No specific emerging SARS-CoV-2 nonsynonymous amino acid changes indicating signatures of viral escape were enriched in those receiving SNG001. These in vivo data provide an intriguing signal that exogenous interferon-β1a may restrict SARS-CoV-2 viral diversity and add to growing evidence that interferon levels play a critical role in antiviral responses during COVID-19.IMPORTANCESARS-CoV-2 encodes several genes which can antagonize the interferon signaling cascade, preventing it from activating antiviral responses and thereby facilitating viral establishment and dissemination. It is unknown how the administration of exogenous interferon might affect viral evolution and immune escape. ACTIV-2/A5401 represents a unique opportunity to study the virologic effects of interferon treatment in a rigorous randomized, placebo-controlled clinical trial setting. Our characterization of longitudinal nasal samples shows that interferon-treated individuals had lower viral diversity and no evidence of viral escape mutations.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04518410.

Humans↗

PubMed2026

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex® database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans↗

PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗

PubMed2026

Acrocomia aculeata (Mbokaja) Kernel Oil Inhibits Herpes Simplex Virus 1 Replication and Promotes Cutaneous Wound Healing in Infected Mice.

Background/Objectives: Herpes simplex virus type 1 (HSV-1) is a global and prevalent pathogen, presenting significant clinical challenges because of its recurring infections, the development of drug resistance and severe clinical complications. This study evaluated the antiviral efficacy against HSV-1 of Acrocomia aculeata (A. aculeata) kernel oil, a Neotropical palm native to the Americas. Methods: The chemical profile of A. aculeata kernel oil was determined by gas chromatography with flame ionization detection (GC-FID). Antiviral activity was assessed using dose-response curves, time-of-addition assays, and quantification of intracellular viral genomes, viral gene transcripts, and IL-6 expression. A. aculeata kernel oil's antiviral effect was also evaluated using an in vivo HSV-1 cutaneous infection model. Results: GC-FID analysis revealed lauric, oleic, and myristic acids as predominant components in the kernel oil. A. aculeata kernel oil exhibited potent antiviral activity against HSV-1. The oil inhibited HSV-1 early step post-entry, reducing the mRNA levels of the immediate-early genes ICP4 and ICP22, leading to the downregulation of early and late viral gene expression and intracellular viral genome. Furthermore, the oil suppressed IL-6 expression in infected cells. Importantly, A. aculeata kernel oil promoted the healing of cutaneous lesions in HSV-1-infected mice. Conclusions: These findings demonstrate that A. aculeata kernel oil is a promising candidate for developing novel antiviral and topical therapies against HSV-1.

Animals↗

PubMed2026

AP2: an indispensable host factor in virus infection.

Adaptor protein complex 2 (AP2), a central regulator of clathrin-mediated endocytosis and intracellular cargo trafficking, is hijacked by numerous viruses to complete their infectious cycles. This review systematically synthesizes the multifaceted roles of AP2 across the entire viral life cycle, from entry and replication to assembly and release, as well as in immune evasion. By delineating how diverse viruses exploit this key host machinery, we further consolidate the rationale and current progress in developing broad-spectrum antiviral strategies that target AP2 and its regulatory pathways. This work aims to provide a unified perspective on AP2 as a critical host-pathogen interface, offering new insights into viral pathogenesis and antiviral drug discovery.

Humans↗

PubMed2025

Bergamottin, A Natural Bioactive Compound, Inhibits Dabie Bandavirus Infection In Vitro and In Vivo.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel, highly fatal disease caused by Dabie bandavirus (DBV), also referred to as severe fever with thrombocytopenia syndrome virus (SFTSV). DBV is endemic to many Asian countries, and its incidence has recently increased. However, there are currently no specific therapies for combating DBV infection. Here we verified whether the natural bioactive compound, bergamottin, effectively inhibits DBV in vitro and in vivo. A primary in vitro study suggested that bergamottin suppressed DBV infection both in Vero E6 and Huh-7 cells in a dose-dependent manner. Time-of-addition assay revealed that bergamottin interferes with DBV infection at multiple stages of the viral life cycle. Moreover, bergamottin inhibits viral internalization and effectively reduces viral genome replication. The efficacy of bergamottin at doses of 75 and 120 mg/kg/d against DBV infection in an IFNAR-/- mouse infection model was investigated. Oral delivery at a dose of 120 mg/kg/d significantly reduced the number of the viral RNA copies in the kidneys, spleen, and lungs. These findings highlight that bergamottin is a promising agent that could be further developed as a therapeutic agent against DBV infection.

Animals↗

PubMed2026

Identification and functional characterization of a novel antiviral chicken interferon-υ.

Interferons are critical mediators of antiviral immunity in vertebrates. While type IV interferon (IFN-υ) has been identified in fish and amphibians, its existence and function in chickens remained unknown. Through systematic genomic screening, we identified and cloned a novel chicken interferon gene, designated ChIFN-υ. Phylogenetic analysis placed ChIFN-υ within a distinct clade alongside zebrafish and clawed frog IFN-υ, confirming its identity as a type IV interferon, with minimal homology to classical type I, II, or III IFNs. Expression profiling revealed constitutive ChIFN-υ expression in mucosal and immune tissues of healthy chickens, exhibiting a distinct developmental shift: highest in trachea and small intestine in 1-day-old chicks, shifting to spleen and lung in 4-week-old chickens. ChIFN-υ expression was strongly upregulated following H9N2 AIV infection. Functionally, recombinant ChIFN-υ protein activated the interferon-stimulated response element (ISRE) and Mx promoter in a dose-dependent manner and significantly inhibited the replication of both vesicular stomatitis virus (VSV) and H9N2 AIV in DF-1 cells. In vivo, early treatment with exogenous ChIFN-υ significantly reduced pulmonary and tracheal viral loads and decreased oropharyngeal and cloacal virus shedding in H9N2-infected chickens. In conclusion, this study identifies and functionally characterizes the type IV interferon in chickens, elucidating the evolutionary status, regulated expression, and antiviral efficacy of ChIFN-υ. These findings highlight its potential as a candidate for developing interferon-based therapies against avian viral diseases.

Animals↗

PubMed2026

Coxsackievirus A6 on the rise: epidemiology, pathogenicity, evolutionary dynamics, and antiviral strategy.

SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

Humans↗

PubMed2024

Conservation of antiviral systems across domains of life reveals immune genes in humans.

Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.

Humans↗

PubMed2026

Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit.

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus for which no specific antiviral therapy is currently available. During the large outbreak in Foshan, Guangdong Province, China, in July 2025, CHIKV rapidly spread to neighboring regions and caused more than 16,000 confirmed cases. In this study, the predominant outbreak strain of CHIKV was selected as the reference sequence to establish a panel of complementary biosafe tools for antiviral compound screening and mechanistic investigation. A virus replicon particle (VRP) system for CHIKV was first constructed and applied to compound library screening, resulting in the identification of three candidate antiviral compounds: MDL-12330A, bazedoxifene acetate, and anidulafungin. To further validate their antiviral activities and investigate their potential mechanisms, CHIKV functional evaluation systems were subsequently established, including vesicular stomatitis virus (VSV)- and murine leukemia virus (MLV)-based pseudovirus systems for viral entry, a replicon RNA system for post-entry replication-associated processes, a replication-defective nsP4 mutant replicon RNA system for primary translation, and a virus-like particle (VLP) system for viral particle assembly and budding assessment. Using these complementary systems, we systematically evaluated the antiviral profiles of the three candidate compounds across multiple stages of the CHIKV life cycle. This analysis revealed distinct stage-specific inhibitory patterns and provided insights into their potential antiviral mechanisms, which warrant validation using authentic CHIKV infection to assess their translational potential.

Chikungunya virus↗

PubMed2025

A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity.

Chikungunya is a mosquito-borne viral disease that causes fever and severe joint pain for which there is no direct acting drug treatments. Vinyl sulfone SGC-NSP2PRO-1 (3) was identified as a potent inhibitor of the nsP2 cysteine protease (nsP2pro) that reduced viral titer against infectious isolates of Chikungunya and other alphaviruses. The covalent warhead in 3 captured the active site C478 and inactivated nsP2pro with a kinact/Ki ratio of 5950 M-1 s-1. The vinyl sulfone 3 was inactive across a panel of 23 other cysteine proteases and demonstrated remarkable proteome-wide selectivity by two chemoproteomic methods. A negative control analog SGC-NSP2PRO-1N (4) retained the isoxazole core and covalent warhead but demonstrated > 100-fold decrease in enzyme inhibition. Both 3 and 4 were stable across a wide range of pH in solution and upon prolonged storage as solids. Vinyl sulfone 3 and its negative control 4 will find utility as high-quality chemical probes to study the role of the nsP2pro in cellular studies of alphaviral replication and virulence.

Chikungunya virus↗