Antiviral research最新文献_第3页

Identification of claramine and anidulafungin as entry inhibitors of Crimean–Congo hemorrhagic fever virus 克里米亚-刚果出血热病毒入境抑制剂克拉拉胺和抗磺胺酮的鉴定

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2026-01-08 DOI: 10.1016/j.antiviral.2026.106343

Yasuteru Sakurai , Minato Hirano , Sayaka Okada , Yohei Kurosaki , Rokusuke Yoshikawa , John N. Barr , Roger Hewson , Kentaro Yoshii , Jiro Yasuda

{"title":"Identification of claramine and anidulafungin as entry inhibitors of Crimean–Congo hemorrhagic fever virus","authors":"Yasuteru Sakurai , Minato Hirano , Sayaka Okada , Yohei Kurosaki , Rokusuke Yoshikawa , John N. Barr , Roger Hewson , Kentaro Yoshii , Jiro Yasuda","doi":"10.1016/j.antiviral.2026.106343","DOIUrl":"10.1016/j.antiviral.2026.106343","url":null,"abstract":"<div><div>Crimean–Congo hemorrhagic fever virus (CCHFV) is a tick-borne enveloped virus that causes a severe disease in humans. Despite its wide geographic distribution, no approved vaccines or therapeutics exist. In this study, we achieved high-titer production of pseudotyped virus bearing CCHFV glycoproteins with a C-terminal truncation. Screening over 3,600 small compounds using this pseudotyped virus identified claramine and anidulafungin as CCHFV entry inhibitors. These hit compounds, as well as caspofungin, which is related to anidulafungin, inhibited pseudotyped viral infection in human liver cells and vascular endothelial cells. They inhibited infection of pseudotyped virus with glycoproteins from various CCHFV strains and Hazara virus, a nairovirus closely related to CCHFV. Using a quantitative fusion assay, the identified inhibitors were shown to block membrane fusion via CCHFV glycoproteins. Moreover, they inhibited infection of replication-competent Hazara virus. Therefore, the assays developed in this study were successful in identifying CCHFV entry inhibitors that target membrane fusion.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106343"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An orally available peptidomimetic with broad-spectrum antiviral activity targeting the enterovirus 2C helicase 具有广谱抗病毒活性的口服拟肽，靶向肠病毒2C解旋酶

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2026-01-02 DOI: 10.1016/j.antiviral.2025.106341

Chang Wang , Huoyan Tong , Xi Zhou , Yuan Fang

{"title":"An orally available peptidomimetic with broad-spectrum antiviral activity targeting the enterovirus 2C helicase","authors":"Chang Wang , Huoyan Tong , Xi Zhou , Yuan Fang","doi":"10.1016/j.antiviral.2025.106341","DOIUrl":"10.1016/j.antiviral.2025.106341","url":null,"abstract":"<div><div>Enteroviruses (EVs) are significant human pathogens, and the development of orally available, broad-spectrum antiviral agents remains an urgent need. The viral protein 2C, a conserved nonstructural protein with helicase activity, is a promising target for antiviral intervention. Although the peptide 2CL was previously identified as a 2C inhibitor, its cell-penetrating peptide motif and extended core sequence may limit its binding efficiency and pharmacological properties. Here, we report the optimization of 2CL to develop a novel peptidomimetic, 2CA-1, with a more compact structure and absence of a cell-penetrating motif. Besides its potent cellular antiviral activity, achieved by precise docking into the 2C binding pocket to inhibit helicase function, 2CA-1 exhibited excellent oral bioavailability in a murine model, significantly reducing viral loads and showing broad efficacy against multiple enteroviruses including CV-A6, CV-A16, CV-B3, Echo11, EV-D68 and rhinovirus. This study not only presents 2CA-1 as an optimized 2C-targeted antiviral candidate but also highlights its potential as an orally available and broad-spectrum therapeutic against EVs.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106341"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-level viremia increases the risk of adverse long-term outcomes in entecavir-treated patients with chronic hepatitis B 低水平病毒血症增加恩替卡韦治疗的慢性乙型肝炎患者不良长期结局的风险。

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI: 10.1016/j.antiviral.2025.106334

Dong Ji , Meng-Wen He , Wen-Chang Wang , Wei Han , Yan Chen , Yan Liu , Le Li , Xu-Yang Li , Yi-Fan Guo , Wu-Cai Yang , Zheng Dong , Chun-Yan Wang , Jing Xu , Lin Tan , George Lau , Yongping Yang

{"title":"Low-level viremia increases the risk of adverse long-term outcomes in entecavir-treated patients with chronic hepatitis B","authors":"Dong Ji , Meng-Wen He , Wen-Chang Wang , Wei Han , Yan Chen , Yan Liu , Le Li , Xu-Yang Li , Yi-Fan Guo , Wu-Cai Yang , Zheng Dong , Chun-Yan Wang , Jing Xu , Lin Tan , George Lau , Yongping Yang","doi":"10.1016/j.antiviral.2025.106334","DOIUrl":"10.1016/j.antiviral.2025.106334","url":null,"abstract":"<div><div>Low-level viremia (LLV) still occurs in some patients with chronic hepatitis B (CHB) after entecavir (ETV) treatment. We aimed to evaluate the effects of LLV on the adverse long-term outcomes. A secondary analysis of a multicenter prospective cohort study, consisting patients who underwent liver biopsy and received entecavir treatment, was conducted. LLV was defined as detectable HBV DNA levels (20–2000 IU/mL) at week 48 after the imitation of ETV treatment, maintained complete virological response (CVR) was defined as HBV DNA <20 IU/mL. The zero time was defined as the date of LLV diagnosis, the primary endpoint was the occurrence of HCC. The time-to-event analyses were performed using log-rank analysis, and multivariable COX regression. The inverse probability of treatment weighting and propensity score matching were used in the sensitivity analyses. In total, 766 patients were enrolled in the final analysis, and LLV was found in 182 patients (23.8 %). Patients with LLV had a significantly higher 7-year cumulative incidence of HCC (18.7 % vs. 8.1 %, <em>p</em> < 0.001) and fibrosis progression rate (17.5 % vs. 8.7 %, <em>p</em> = 0.017) than those with CVR. Multivariate analysis identified LLV as an independent risk factor associated with HCC (adjusted HR: 3.935; 95 % CI: 2.218–6.979, <em>p</em> < 0.001) and fibrosis progression (adjusted OR 5.342; 95 % CI: 1.630–17.480, <em>p</em> = 0.006). A nomogram incorporating LLV, age, PLT and liver cirrhosis was developed and validated for HCC risk prediction, demonstrating excellent performance with a C-index of 0.778. In conclusion, LLV significantly promoted HCC occurrence and fibrosis progression in CHB patients receiving anti-HBV treatment.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106334"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-shot design of a cyclic peptide inhibitor of HIV membrane fusion HIV膜融合环肽抑制剂的单次设计。

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2025-12-20 DOI: 10.1016/j.antiviral.2025.106336

Diandra Daumiller , Federica Giammarino , Qiuzhen Li , Anders Sönnerborg , Rafael Ceña Diez , Patrick Bryant

{"title":"Single-shot design of a cyclic peptide inhibitor of HIV membrane fusion","authors":"Diandra Daumiller , Federica Giammarino , Qiuzhen Li , Anders Sönnerborg , Rafael Ceña Diez , Patrick Bryant","doi":"10.1016/j.antiviral.2025.106336","DOIUrl":"10.1016/j.antiviral.2025.106336","url":null,"abstract":"<div><div>HIV evades immune detection through rapid mutation of its surface proteins, yet essential steps in viral entry, such as CD4 and co-receptor engagement, remain highly conserved. While therapies like Lenacapavir represent major advances, the emergence of resistant strains highlights the urgent need for adaptable, rapid-response antivirals. This challenge extends beyond HIV, demanding scalable design strategies for diverse viral threats. Here, we demonstrate that AI-driven design can address this need by generating cyclic peptide binders targeting a previously unexploited interface on the HIV-1 fusion protein gp41. Using only sequence information, without prior structural or binding site data, we designed and experimentally validated a single candidate. This inhibitor potently blocked infection by two HIV-1 strains in cell-based assays with no detectable cytotoxicity. Affinity analysis with SPR confirms the interaction with gp41 as designed. Our findings illustrate how AI-guided peptide design, coupled with rapid in-vitro validation, can accelerate early-stage therapeutic discovery and enable timely intervention against emerging viral threats.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106336"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A new locus of foscarnet resistance in the cytomegalovirus UL54 DNA polymerase gene among uncharacterized mutations in recent clinical trials 在最近的临床试验中，巨细胞病毒UL54 DNA聚合酶基因在未表征的突变中发现了新的膦酸钠耐药位点。

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2025-12-31 DOI: 10.1016/j.antiviral.2025.106340

Sunwen Chou , Alexis Minyard , Justin Watanabe

{"title":"A new locus of foscarnet resistance in the cytomegalovirus UL54 DNA polymerase gene among uncharacterized mutations in recent clinical trials","authors":"Sunwen Chou , Alexis Minyard , Justin Watanabe","doi":"10.1016/j.antiviral.2025.106340","DOIUrl":"10.1016/j.antiviral.2025.106340","url":null,"abstract":"<div><div>In two recent Phase 3 clinical trials of maribavir that also involved existing standard therapies, many uncharacterized cytomegalovirus UL54 DNA polymerase genetic variants were encountered. Six UL54 mutations were selected for phenotyping, based on proximity to published resistance loci and quality of sequencing information. UL54 amino acid substitutions E949K and E949Q conferred foscarnet resistance with slightly decreased ganciclovir and cidofovir susceptibility, representing a novel palm domain resistance locus. UL54 N498S and P598S mutants had slight decreases in ganciclovir and cidofovir susceptibility, with N498S also having a slightly decreased foscarnet susceptibility. No drug resistance was attributed to A786V and A928V. Retesting published phenotypes for UL54 mutants D515E, D542E, A543V and A928T revealed some discordant findings, including ganciclovir resistance for D542E and A543V, and no drug resistance for D515E and A928T. These genotype-phenotype correlations add to the evidence base for clinical diagnostic testing of cytomegalovirus drug resistance.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106340"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

2-Deoxy-D-glucose attenuates lipopolysaccharide-induced inflammation and restricts Zika, Chikungunya, and Mayaro virus replication in monocyte-derived macrophages 2-脱氧-d -葡萄糖减轻脂多糖诱导的炎症，并限制寨卡病毒、基孔肯雅病毒和玛雅罗病毒在单核细胞来源的巨噬细胞中的复制

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.antiviral.2025.106338

Y.S. Tamayo-Molina, Yisel García-Marin, Silvio Urcuqui-Inchima

{"title":"2-Deoxy-D-glucose attenuates lipopolysaccharide-induced inflammation and restricts Zika, Chikungunya, and Mayaro virus replication in monocyte-derived macrophages","authors":"Y.S. Tamayo-Molina, Yisel García-Marin, Silvio Urcuqui-Inchima","doi":"10.1016/j.antiviral.2025.106338","DOIUrl":"10.1016/j.antiviral.2025.106338","url":null,"abstract":"<div><div>Re-emerging arthropod-borne viruses such as Mayaro (MAYV), Chikungunya (CHIKV), and Zika (ZIKV) pose a growing global health concern as <em>Aedes</em> mosquito populations expand. These arboviruses infect innate immune cells, particularly monocyte-derived macrophages (MDMs), which support viral replication and serve as reservoirs that facilitate dissemination. Because no effective antiviral treatments are available, strategies that modulate macrophage responses and restrict viral replication are urgently needed. Here, we evaluated the immunomodulatory and antiviral effects of 2-deoxy-D-glucose (2-DG) in human MDMs. First, we assessed how 2-DG shapes transcriptional responses to lipopolysaccharide (LPS), a canonical TLR4 agonist. Co-treatment with 2-DG and LPS induced genes linked to inflammatory, antiviral, and endoplasmic reticulum (ER) stress pathways. Notably, IL10 mRNA and IL-10 protein displayed an inverse relationship with metabolic stress yet correlated positively with inflammatory and antiviral gene expression, whereas GADD34 was positively associated with both inflammatory and ER stress responses, suggesting an integrative regulatory role. We next investigated whether 2-DG pretreatment limits replication of MAYV, CHIKV, and ZIKV in infected MDMs. Antiviral assays demonstrated that 2-DG reduced replication of all three arboviruses by approximately one log<sub>10</sub>. Additional analyses revealed distinct temporal sensitivities: MAYV and CHIKV showed early and late susceptibility, whereas ZIKV exhibited a distinct kinetic profile. Mechanistic experiments confirmed that 2-DG acts post-entry primarily and reverses the antiviral phenotype observed in LPS-primed MDMs. Collectively, these findings reveal crosstalk among inflammatory, antiviral, and ER stress pathways and demonstrate that 2-DG modulates LPS-driven inflammation while reducing replication of pathogenic arboviruses in human MDMs.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106338"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Newcastle disease virus TS09-C strain provides long-lasting protection against virulent strain after in-ovo immunization 新城疫病毒TS09-C毒株在卵内免疫后对毒力毒株具有持久的保护作用。

IF 4 2区医学

Antiviral research Pub Date : 2026-02-01 Epub Date: 2025-12-10 DOI: 10.1016/j.antiviral.2025.106325

Helong Feng , Junjie Yang , Liren Jiang , Xiaoyu Suo , Yuqiao Zhu , Yu Shang , Hongcai Wang , Zhe Zeng , Lun Yao , Qingping Luo , Guoyuan Wen

{"title":"Newcastle disease virus TS09-C strain provides long-lasting protection against virulent strain after in-ovo immunization","authors":"Helong Feng , Junjie Yang , Liren Jiang , Xiaoyu Suo , Yuqiao Zhu , Yu Shang , Hongcai Wang , Zhe Zeng , Lun Yao , Qingping Luo , Guoyuan Wen","doi":"10.1016/j.antiviral.2025.106325","DOIUrl":"10.1016/j.antiviral.2025.106325","url":null,"abstract":"<div><div>Newcastle disease (ND) is an important infectious disease in poultry, causing substantial economic losses in many countries. Vaccination with live vaccines is a common strategy for ND control, and farmers generally vaccinate multiple times each year because the current ND vaccines have a relatively short protection period. Here, we report that the NDV strain TS09-C, as an <em>in ovo</em> vaccine, provided long-lasting protection for at least 12 months against virulent NDV. TS09-C significantly reduced the tissue viral titer, alleviated histopathological lesions, and induced proliferation of CD8<sup>+</sup> T cells after challenge. TS09-C <em>in ovo</em> group vs PBS group, 142 immune-related DEGs were screened based on RNA-Seq, including 18 up-regulated DEGs and 124 down-regulated DEGs. The innate immune pathways of these genes, as NOD-like, Toll-like, RIG-I-like, Cytokine-cytokine receptor interaction, and all genes (including pro-inflammatory cytokines IL-1B, IL-6, IL-18, etc) in these pathways were significantly downregulated. These results indicate that NDV strain TS09-C is a long-lasting protection vaccine candidate against ND, and the protection might be due to the reason that TS09-C induces the proliferation of CD8<sup>+</sup> T cells and inhibits the inflammatory response.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"246 ","pages":"Article 106325"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Isochlorogenic acid A impairs hepatitis B virus replication by interference with various steps of hepatitis B virus life cycle involving HO-1-mediated ROS modulation 异绿原酸A通过干扰乙型肝炎病毒生命周期的各个步骤，包括ho -1介导的ROS调节，从而损害乙型肝炎病毒的复制

IF 4 2区医学

Antiviral research Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1016/j.antiviral.2025.106323

Giscard Wilfried Koyaweda , Mirco Glitscher , Anja Schollmeier , Daniela Bender , Eberhard Hildt

{"title":"Isochlorogenic acid A impairs hepatitis B virus replication by interference with various steps of hepatitis B virus life cycle involving HO-1-mediated ROS modulation","authors":"Giscard Wilfried Koyaweda , Mirco Glitscher , Anja Schollmeier , Daniela Bender , Eberhard Hildt","doi":"10.1016/j.antiviral.2025.106323","DOIUrl":"10.1016/j.antiviral.2025.106323","url":null,"abstract":"<div><div>Chronic hepatitis B virus (HBV) infection is a major health problem, affecting around 254 million people worldwide. Current treatments have side effects and can lead to resistance. Therefore, natural compounds derived from plants are being studied as potential antivirals. Isochlorogenic acid A (ICAA), which is derived from caffeoylquinic acid, exerts antiviral and hepatoprotective effects. The antioxidant effect of ICAA, triggered by upregulation of heme oxygenase 1 (HO-1), has been suggested as potential antiviral mechanism. However, the underlying mechanisms remain enigmatic. Our aim is to elucidate the mode of action of the antiviral effect of ICAA on HBV. Stable or transient transfected cells expressing HBV as well as HBV-infected cells were instrumental. (Sub)viral particles were characterized by biophysical and biochemical methods. Subcellular distribution of viral proteins was studied using confocal laser scanning microscopy. Viral genomes and transcripts were quantified by qPCR.</div><div>Treatment with ICAA decreased levels of HBV surface and e antigens (HBsAg and HBeAg), as well as viral transcripts, genomes and most important cccDNA. Furthermore, impaired virus assembly was evident from accumulation of naked capsids suggesting improper capsid formation and impaired envelopment. ICAA-dependent effects on HBV correlate with upregulation of HO-1 and modulation of intracellular ROS Our data indicate a possible link between changes in the intracellular ROS level and altered free -SH groups in viral structural proteins, possibly influencing proper disulphide bond formation and thereby assembly. In conclusion ICAA-dependent effects on HBV life cycle are based on several pillars as modulation of intracellular ROS and impaired morphogenesis and replication.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"245 ","pages":"Article 106323"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

JC polyomavirus-encoded miRNA jcv-miR-J1-5p downregulates BK polyomavirus infection JC多瘤病毒编码miRNA jv - mir - j1 -5p下调BK多瘤病毒感染

IF 4 2区医学

Antiviral research Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.antiviral.2025.106313

Baptiste Demey , Aurélien Aubry , Virginie Morel , Louison Collet , Catherine Francois , Sandrine Castelain , Francois Helle , Etienne Brochot

{"title":"JC polyomavirus-encoded miRNA jcv-miR-J1-5p downregulates BK polyomavirus infection","authors":"Baptiste Demey , Aurélien Aubry , Virginie Morel , Louison Collet , Catherine Francois , Sandrine Castelain , Francois Helle , Etienne Brochot","doi":"10.1016/j.antiviral.2025.106313","DOIUrl":"10.1016/j.antiviral.2025.106313","url":null,"abstract":"<div><div>BK and JC Polyomavirus are closely related and establish persistence in infected subjects. Recent studies suggest that JC Polyomavirus replication prevents BK Polyomavirus-related pathologies in kidney transplant recipients. One potential mechanism of this competition could involve viral microRNAs cross-reacting, as they are highly homologous between species. In fact, bkv-miR-B1-3p is strictly identical to jcv-miR-J1-3p, whereas species-specific miRNAs bkv-miR-B1-5p and jcv-miR-J1-5p differ barely.</div><div>Early detection of jcv-miR-J1-5p in urine significantly reduces the risk of BK Polyomavirus DNAemia in kidney transplant recipients in a case-control study including 39 patients (odds ratio [95 % Confidence Interval] = 0.00 [0.00–0.65], p = 0.012). <em>In vitro</em> modeling revealed that prior infection with JC Polyomavirus reduces the ability of BK Polyomavirus to grow in immortalized human renal proximal tubular epithelial cells, without significant expression of JC Polyomavirus proteins. The JC Polyomavirus-specific miRNA jcv-miR-J1-5p was discovered to decrease BK Polyomavirus TAg mRNA expression, without affecting early genome replication, like the known regulatory effect of BK Polyomavirus-encoded bkv-miR-B1-3p and bkv-miR-B1-5p. An archetypal strain of JC Polyomavirus engineered to quench miRNA maturation did not inhibit BK Polyomavirus infection, unlike the wild-type strain, confirming that the inhibitory effect of JC Polyomavirus is due to miRNAs.</div><div>These results suggest that JC Polyomavirus-specific miRNA jcv-miR-J1-5p limits BK Polyomavirus infectivity and early TAg expression, with an intensity similar to BK Polyomavirus miRNAs. This mechanism might explain <em>in vivo</em> competition for viral replication between BK Polyomavirus and JC Polyomavirus infections.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"245 ","pages":"Article 106313"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Poly (allylamine hydrochloride)-selenium nanoparticles inhibit porcine reproductive and respiratory syndrome virus by targeting DDX5 and reactive oxygen species 聚丙烯胺-硒纳米粒子对猪繁殖与呼吸综合征病毒DDX5和活性氧的抑制作用

IF 4 2区医学

Antiviral research Pub Date : 2026-01-01 Epub Date: 2025-12-05 DOI: 10.1016/j.antiviral.2025.106324

Wenqiao Yang , Yuan Xu , Runmin Kang , Min Zhang , Yuting Zhang , Zeng Yang , Huiyuan Jing , Yilin Liu , Jiaxiang Li , Yongjie Ge , Haibo Feng , Long Zhou , Jiang Pi , Jie Liu

{"title":"Poly (allylamine hydrochloride)-selenium nanoparticles inhibit porcine reproductive and respiratory syndrome virus by targeting DDX5 and reactive oxygen species","authors":"Wenqiao Yang , Yuan Xu , Runmin Kang , Min Zhang , Yuting Zhang , Zeng Yang , Huiyuan Jing , Yilin Liu , Jiaxiang Li , Yongjie Ge , Haibo Feng , Long Zhou , Jiang Pi , Jie Liu","doi":"10.1016/j.antiviral.2025.106324","DOIUrl":"10.1016/j.antiviral.2025.106324","url":null,"abstract":"<div><div>Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) remains a critical threat to the swine industry worldwide due to its rapid evolution and limited vaccine efficacy. In this study, we synthesized and characterized poly (allylamine hydrochloride)-selenium nanoparticles (PAH-Se NPs) and evaluated their antiviral activity against PRRSV in vitro and the underlying mechanism. PAH-Se NPs exhibited uniform spherical morphology with average hydrodynamic diameter of 118 nm and excellent colloidal stability with a zeta potential of +50.7 mV. Cytotoxicity assays demonstrated low toxicity of PAH-Se NPs in MARC-145 cells with a CC<sub>50</sub> of 40.24 μg/mL, indicating favorable biocompatibility. Multiple complementary assays, including viral RNA quantification, cell viability restoration, plaque assays, N protein expression analyses, and indirect immunofluorescence assay, showed that PAH-Se NPs could significantly inhibit PRRSV replication in a dose-dependent manner, with an IC<sub>50</sub> of 0.076 μg/mL. Moreover, this inhibition was equally effective against other sub-genotypes of PRRSV, including VR2332 and NADC30-like variants, as well as the DNA virus and bacteria, indicating the broad-spectrum anti-microbial properties of PAH-Se NPs. Mechanistic studies indicated that PAH-Se NPs target viral invasion and replication by down-regulating the host factor DDX5, which interacts with PRRSV Nsp9 to facilitate viral RNA synthesis, and suppressed PRRSV-induced reactive oxygen species (ROS) accumulation. This work emphasized PAH-Se NPs as a potent, low-toxicity antiviral candidate, offering promising potential for the development of alternative therapeutics against PRRSV and related viral infections.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"245 ","pages":"Article 106324"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0