Antiviral researchPub Date : 2025-07-22DOI: 10.1016/j.antiviral.2025.106240
Hao Zhang, Ziyang Sheng, Feiyang Xue, Han Wang, Na Gao, Shiqi He, Yuetong Li, Dongying Fan, Peigang Wang, Lei Yu, Jing An
{"title":"Single-Dose Injection of Human Neutralizing Antibody Against ZIKV Preserves Male Fertility and Protects against Lethal Infection.","authors":"Hao Zhang, Ziyang Sheng, Feiyang Xue, Han Wang, Na Gao, Shiqi He, Yuetong Li, Dongying Fan, Peigang Wang, Lei Yu, Jing An","doi":"10.1016/j.antiviral.2025.106240","DOIUrl":"https://doi.org/10.1016/j.antiviral.2025.106240","url":null,"abstract":"<p><p>Zika virus (ZIKV) is a mosquito-transmitted flavivirus. Unlike other flavivirus members, ZIKV has a distinct tropism for the reproductive system. Previous studies have demonstrated that ZIKV has adverse impacts on the male reproductive system, particularly in testis and epididymis. However, no specific prophylactic and therapeutic agents are available against ZIKV till now. A human monoclonal antibody, 2B10, has been shown to be protective against microcephaly. Here, we intraperitoneally administered a single injection of 2B10 after ZIKV infection to explore its therapeutic potential on viral damage in testis and epididymis in both IFN-α/β and IFN-γ receptor-deficient (AG6) mouse and IFN-α/β receptor-deficient (A6) mouse models. The results showed that 2B10 significantly decreased the viremia and viral loads in organs in two types of male mice, markedly mitigated ZIKV-induced histo-morphologic disruption and inflammatory infiltration and maintained hormone levels. The integrity of tight junctions in the testis and epididymis was also maintained at normal levels by 2B10 administration. In long-term observation in ZIKV-infected A6 mice, 2B10 could confer effective protection of male fertility. In the AG6 model, 2B10 fully protected mice from lethal challenge. These results suggested that 2B10 provides effective protection in post-exposure therapy for ZIKV infection in mice. Since 2B10 is a human antibody, it might be a promising intervention candidate for maintaining male reproductive health during ZIKV infection in the endemic area.</p>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106240"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697463","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}
Antiviral researchPub Date : 2025-07-21DOI: 10.1016/j.antiviral.2025.106241
Danya Medina-Carrasco , Glay Chinea Santiago , Hilda Elisa Garay Pérez , Gladys Gutiérrez-Bugallo , Luis Gabriel González-Lodeiro , Anubis Vega-Rúa , Vivian Huerta Galindo
{"title":"Mammalian-targeted antiviral peptide reduces dengue virus type 1 infection in Aedes aegypti","authors":"Danya Medina-Carrasco , Glay Chinea Santiago , Hilda Elisa Garay Pérez , Gladys Gutiérrez-Bugallo , Luis Gabriel González-Lodeiro , Anubis Vega-Rúa , Vivian Huerta Galindo","doi":"10.1016/j.antiviral.2025.106241","DOIUrl":"10.1016/j.antiviral.2025.106241","url":null,"abstract":"<div><div>Dengue virus is the most important arbovirus for public health worldwide. <em>Aedes aegypti</em> is the DENV primary vector and acquires the virus during blood meal from a viremic human. BCN0941 is a structure-based designed antiviral peptide that inhibits early stages of DENV infection in mammalian cells [WO2015131858A2]. Studies of structure-activity relationship indicate that the molecular target of the antiviral activity of BCN0941 is the Low-density lipoprotein receptor related protein-1 (LRP1), an evolutionary conserved receptor that we have identified as putative DENV receptor in mammalian cells. In this work, we evaluated the antiviral activity of BCN0941 peptide against DENV serotype 1 in mosquito cells. <em>In vitro</em> assays were performed in cell lines C6/36 (<em>Aedes albopictus</em>) and Aag2 (<em>Aedes aegypti</em>)<em>.</em> The antiviral activity <em>in vivo</em> in a metapopulation of field-collected <em>A. aegypti</em> mosquitoes was also evaluated. BCN0941 peptide exhibited the capacity to decrease viral infection in both experimental set up, <em>in vivo</em> and <em>in vitro</em>, up to a 50 % and 60 % of the treatment controls respectively, as determined by immunofluorescence. BCN0941 may be an effective DENV transmission-blocking drug due to its dual action in decreasing the viral load in infected people and the mosquito vector.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106241"},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678857","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}
Antiviral researchPub Date : 2025-07-21DOI: 10.1016/j.antiviral.2025.106242
Laura Vandemaele, Thibault Francken, Joost Schepers, Winston Chiu, Niels Cremers, Hugo Klaassen, Charlène Marcadet, Lorena Sanchez Felipe, Arnaud Marchand, Patrick Chaltin, Pieter Leyssen, Johan Neyts, Manon Laporte
{"title":"High-throughput split-GFP antiviral screening assay against fusogenic paramyxoviruses.","authors":"Laura Vandemaele, Thibault Francken, Joost Schepers, Winston Chiu, Niels Cremers, Hugo Klaassen, Charlène Marcadet, Lorena Sanchez Felipe, Arnaud Marchand, Patrick Chaltin, Pieter Leyssen, Johan Neyts, Manon Laporte","doi":"10.1016/j.antiviral.2025.106242","DOIUrl":"https://doi.org/10.1016/j.antiviral.2025.106242","url":null,"abstract":"<p><p>The paramyxovirus family includes important pathogens such as measles and mumps viruses, as well as emerging pathogens with pandemic potential such as Nipah virus. Despite the threat to public health and the frequent identification of novel paramyxoviruses, no antiviral drugs are currently available. A hallmark of most paramyxoviruses is the induction of cell-cell fusion leading to syncytia formation. To facilitate antiviral drug discovery, we leveraged this trait and established a high-throughput split-green fluorescent protein (GFP) antiviral screening assay suitable for high-content imaging through the quantification of virus-induced GFP<sup>+</sup> syncytia. The assay was validated with well-known broad-spectrum antiviral compounds against representative members of five different Paramyxovirinae genera. Using this split-GFP assay, a small-molecule repurposing library of approximately 3000 compounds was screened against recombinant Cedar virus, a nonpathogenic henipavirus. Two molecules were identified: Cathepsin Inhibitor 1 with henipavirus-specific activity and PF-543 with pan-paramyxovirus activity. Both molecules inhibit viral replication by blocking cell-cell fusion. The split-GFP assay presented here will enable the development of extensive drug discovery initiatives aimed at identifying much-needed pan-henipavirus/paramyxovirus inhibitors.</p>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106242"},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697462","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}
Antiviral researchPub Date : 2025-07-18DOI: 10.1016/j.antiviral.2025.106239
Satyendu Nandy, Siddharth Neog, Sachin Kumar
{"title":"Cholesterol 25-hydroxylase inhibits Newcastle disease virus replication by its architectural damage and blocking HN protein","authors":"Satyendu Nandy, Siddharth Neog, Sachin Kumar","doi":"10.1016/j.antiviral.2025.106239","DOIUrl":"10.1016/j.antiviral.2025.106239","url":null,"abstract":"<div><div>Cholesterol 25-hydroxylase (CH25H) is a membrane-bound endoplasmic reticulum protein that converts cholesterol into 25-hydroxycholesterol (25HC). Recent studies showed that CH25H is an interferon-stimulated gene (ISG) that helps fight various viruses and has broad antiviral effects. However, the role of chicken CH25H (chCH25H) in controlling Newcastle disease virus (NDV) infection and replication remains unexplored. This study examined the impact of chCH25H on NDV infection in chicken embryo fibroblast cells. The results showed that cells try to upregulate the chCH25H expression temporally upon viral infection. Moreover, the overexpression of chCH25H reduced NDV infection in cells while reducing endogenous chCH25H levels increased its replication. Additionally, treating cells and viruses with 25HC, an active metabolic intermediate of chCH25H, significantly reduced NDV replication by blocking the virus from entering cells while causing significant structural damage to the virus architecture. In addition, <em>in ovo</em> results also exhibited that the eggs treated with lipopolysaccharides (LPS), a positive regulator of chCH25H and 25HC, resulted in extensive viral reduction. These findings indicate that chCH25H and 25HC are against NDV replication in chicken fibroblast cells.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106239"},"PeriodicalIF":4.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673836","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}
Antiviral researchPub Date : 2025-07-15DOI: 10.1016/j.antiviral.2025.106238
Guillermo Albericio , Daniel Rodríguez-Martín , Pablo Avilés , Carmen Cuevas , María J. Guillén-Navarro , María A. Noriega , Sara Flores , Pedro J. Sánchez-Cordón , David Astorgano , Patricia Pérez , Mariano Esteban , Juan García-Arriaza
{"title":"Functional characteristics of plitidepsin as an antiviral treatment against monkeypox virus infection","authors":"Guillermo Albericio , Daniel Rodríguez-Martín , Pablo Avilés , Carmen Cuevas , María J. Guillén-Navarro , María A. Noriega , Sara Flores , Pedro J. Sánchez-Cordón , David Astorgano , Patricia Pérez , Mariano Esteban , Juan García-Arriaza","doi":"10.1016/j.antiviral.2025.106238","DOIUrl":"10.1016/j.antiviral.2025.106238","url":null,"abstract":"<div><div>Monkeypox virus (MPXV), closely related to variola virus, causes mpox, a zoonotic disease traditionally endemic to Central Africa. However, recent outbreaks have increased human transmission of MPXV clades. In 2022, global MPXV spread was linked to clade IIb, whereas in 2024, the more pathogenic clade Ib became predominant. These trends raised concerns about sustained human transmission, prompting the WHO to declare mpox a Public Health Emergency of International Concern. Despite the availability of smallpox vaccines, their protective efficacy against mpox remains limited. Additionally, the limited efficacy of current smallpox antivirals, such as Tecovirimat and Brincidofovir, alongside growing concerns about the emergency of tecovirimat resistance mutants, underscores the need for new therapeutic options. Given these challenges, novel antiviral strategies with different mechanisms of action are urgently needed to control MPXV outbreaks. Plitidepsin, a cyclodepsipeptide drug initially approved for cancer treatment, has demonstrated potent antiviral activity against multiple viruses by targeting eukaryotic elongation factor 1 alpha (eEF1A). Here, we have evaluated the antiviral activity of plitidepsin against MPXV infection. In cultured cells, plitidepsin exhibited strong antiviral effects, with a favorable therapeutic index and low cytotoxicity. In CAST/EiJ mice, a highly susceptible MPXV model, plitidepsin significantly reduced viral replication in the lungs. Additionally, treated mice displayed a marked reduction in inflammatory lung lesions and proinflammatory cytokines, suggesting immunomodulatory effects. These findings indicate plitidepsin as a promising candidate for mpox treatment. Further studies are needed to explore its potential as a standalone or combination therapy, supporting clinical evaluation for mpox treatment.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106238"},"PeriodicalIF":4.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658230","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}
Antiviral researchPub Date : 2025-07-11DOI: 10.1016/j.antiviral.2025.106232
Jianshu Li , Siyu Li , Chaode Gu , Shaowen Shi , Xiao Li , Zhendong Guo , Zongzheng Zhao , Miao He , Zhiwei Wu
{"title":"Pralatrexate effectively inhibits the replication of monkeypox virus in vitro and in vivo","authors":"Jianshu Li , Siyu Li , Chaode Gu , Shaowen Shi , Xiao Li , Zhendong Guo , Zongzheng Zhao , Miao He , Zhiwei Wu","doi":"10.1016/j.antiviral.2025.106232","DOIUrl":"10.1016/j.antiviral.2025.106232","url":null,"abstract":"<div><div>The monkeypox virus (MPXV), an orthopoxvirus, has caused a number of major outbreaks and emerged as a global public health threat. Although drugs have been approved for the treatment of mpox, the efficacy and side effects remain unknown, which calls for the development of safe and effective drugs. Pralatrexate (PDX) is a fourth-generation antifolate drug with inhibitory activity against a wide range of viruses. In this study, we demonstrated the antiviral activity of PDX against MPXV <em>in vitro</em> and <em>in vivo</em>. Our results showed that PDX potently inhibited the MPXV replication at very low drug concentrations <em>in vitro</em>, and could significantly inhibit MPXV activity in dormice. In conclusion, this study found that PDX is an effective antiviral drug against MPXV infection, showing potential as a novel therapy for MPXV infection.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106232"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616058","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}
Antiviral researchPub Date : 2025-07-11DOI: 10.1016/j.antiviral.2025.106237
Meghan F. Carter, Kassidy Knight, Yetunde Kayode, Eain A. Murphy
{"title":"Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling","authors":"Meghan F. Carter, Kassidy Knight, Yetunde Kayode, Eain A. Murphy","doi":"10.1016/j.antiviral.2025.106237","DOIUrl":"10.1016/j.antiviral.2025.106237","url":null,"abstract":"<div><div>Infection with human cytomegalovirus (HCMV) can result in a significant disease burden within the immunosuppressed and immunocompromised patient populations. Current standard of care (SOC) relies on direct-acting antivirals which target a limited group of viral proteins including the viral polymerase (UL54), terminase (UL56), and protein kinase (UL97). Incomplete inhibition of virally encoded proteins result in a selective pressure towards the generation of “breakthrough” drug resistant variants. One limitation in evaluating novel antivirals is the difficulty in profiling their antiviral activity against variants resistant to current SOC interventions, as these resistant variants have arisen in different genetic backgrounds with distinct replication kinetics and yields.</div><div>To limit strain variation we generated a targeted mutant panel of viruses in a bacterial artificial chromosome (BAC) derived clinically relevant laboratory strain of HCMV, TB40e, that expresses the fluorescent proteins mCherry upon viral entry and eGFP at times after viral DNA replication. This unique construct allows for the monitoring of viral entry and viral DNA replication independently. This panel consists of WT and seven mutant viruses harboring mutations that confer resistance to ganciclovir, maribavir, cidofovir, and letermovir. In addition, we characterized a host-targeted sirtuin 2 deacetylase (Sirt2) inhibitor, FLS-359, against the SOC resistant variants. We observed that mutant viruses demonstrated increased EC<sub>50</sub> concentrations for SOC inhibition, and that host directed FLS-359 demonstrated broad-spectrum antiviral activity against known SOC drug-resistant mutants. This panel represents a much-needed comparatively innovative platform for screening the efficacy of new direct-acting antivirals and host-directed antivirals against HCMV variants refractive to therapeutic interventions.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106237"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623823","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}
{"title":"SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody","authors":"Mikhail Lebedin , Nikolai Petrovsky , Kairat Tabynov , Kaissar Tabynov , Yuri Lebedin","doi":"10.1016/j.antiviral.2025.106235","DOIUrl":"10.1016/j.antiviral.2025.106235","url":null,"abstract":"<div><div>Monoclonal antibodies are widely used for the treatment of infectious human diseases, including COVID-19. Since the start of the pandemic, eight monoclonal antibodies against SARS-CoV-2 were granted emergency use authorization. The high mutation rate of the SARS-CoV-2 virus has led to the emergence of highly transmissible variants that can evade vaccine-induced immunity. In this study, we generated a panel of murine monoclonal antibodies (mAb) to identify a subset that broadly neutralized SARS-CoV-2 variants and explored whether mucosal administration of such antibodies could protect against infection. Intranasal delivery of XR10, the most promising murine mAb, protected hamsters against infection by Delta variant. We next humanized XR10 mAb using a combination of CDR-grafting and Vernier zones preservation approaches (CRVZ) to create a panel of humanized XR10 variants. We ranked the variants based on their spike binding ability and virus neutralization. Of these, XR10v48 demonstrated the best ability to neutralize SARS-CoV-2 variants and was protective in hamsters when given as a single 50 μg/kg intranasal dose at the time of viral challenge. XR10v48 featured 34 key amino acid residues retained from the murine progenitor. With SARS-CoV-2 escape mutants continuing to emerge this work highlights a potential workflow to generate humanized broadly cross-neutralizing mAb for potential use as a nasal spray for SARS-CoV-2 prophylaxis.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106235"},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616059","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}
{"title":"Decreased CD4+ T cell counts drive aberrant B cell repertoire alterations in people living with HIV","authors":"Lina Huang , Xiangyu Zhang , Yu Shi , Rishen Liang , Qianqian Chen , Jing Yang , Xiaoni Zhang , Anning Fang , Qian Zhang , Chengchao Ding , Jiabin Wu , Jianjun Wu , Yong Gao","doi":"10.1016/j.antiviral.2025.106236","DOIUrl":"10.1016/j.antiviral.2025.106236","url":null,"abstract":"<div><div>Understanding the evolution of broadly neutralizing antibody (bNAb) activity in people living with HIV is crucial for vaccine design and immunization strategies. It has been proposed that antibody cross-reactive activity is associated with lower CD4<sup>+</sup> T cell counts during people living with HIV, but the underlying mechanisms remain unclear. To further explore the correlation between antibody reactivity and CD4<sup>+</sup> T cell counts, we recruited people living with HIV with varying CD4<sup>+</sup> T cell counts: (i) CD4<sup>+</sup> T cell ≤50 cells/μL, (ii) 50 cells/μL < CD4<sup>+</sup> T cell ≤200 cells/μL, (iii) 200 cells/μL < CD4<sup>+</sup> T cell ≤500 cells/μL, (iv) 500 cells/μL < CD4<sup>+</sup> T cell. We assessed the antigen-specific antibodies in serum using SOSIP.664 trimers from four different subtypes. Immune repertoire sequencing was used to characterize the B cell receptor (BCR) repertoire of these individuals. The evaluation of antigen-specific antibodies with different SOSIP.664 trimers showed enhanced reactivity in individuals with low CD4<sup>+</sup> T cell counts compared to those with high/normal CD4<sup>+</sup> T cell counts. Analysis of antibody gene repertoires through BCR high throughput sequencing revealed an increased proportion of IgG with heavy chain complementarity-determining region 3 (CDRH3) loops exceeding 20 amino acids in individuals with CD4<sup>+</sup> T cell counts below 50 cells/μL. Notably, the IGHV1-46 and IGHV4-34 germlines, which are suggestive of most polyreactive B cells, were preferentially used in individuals with low CD4<sup>+</sup> T cell counts. These results suggest that limited engagement of CD4<sup>+</sup> T cells could facilitate the survival of aberrant B cell repertoire with long CDRH3 regions.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106236"},"PeriodicalIF":4.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607247","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}
Antiviral researchPub Date : 2025-07-05DOI: 10.1016/j.antiviral.2025.106234
Yi-Fan Guo , Yihui Rong , Yan-Ping Chen , Song Yang , Guangde Zhou , Xiao-Xia Niu , Xiao-Huan Wu , Yue-Ran Liu , Wen-Jing Zhang , Le Li , Yan Liu , Wen-Chang Wang , Xu-Yang Li , Chun-Yan Wang , Wucai Yang , Chang Guo , Lin Tan , Fu-Sheng Wang , Dong Ji
{"title":"Assessment of significant hepatic damage in young patients with chronic hepatitis B to initiate the antiviral treatment: The APLB score","authors":"Yi-Fan Guo , Yihui Rong , Yan-Ping Chen , Song Yang , Guangde Zhou , Xiao-Xia Niu , Xiao-Huan Wu , Yue-Ran Liu , Wen-Jing Zhang , Le Li , Yan Liu , Wen-Chang Wang , Xu-Yang Li , Chun-Yan Wang , Wucai Yang , Chang Guo , Lin Tan , Fu-Sheng Wang , Dong Ji","doi":"10.1016/j.antiviral.2025.106234","DOIUrl":"10.1016/j.antiviral.2025.106234","url":null,"abstract":"<div><div>Whether patients aged ≤30 years with chronic hepatitis B (CHB) and normal alanine transaminase (ALT) levels (<40 U/L) should receive antiviral therapy is controversial. In this study, we aimed to identify high-risk factors of significant hepatic damage (SHD) and established a scoring system to guide the decision to administer antiviral treatment. Eligible patients who underwent a liver biopsy were retrospectively screened and randomly assigned to either a training or validation set. Hepatic fibrosis (S0-4) and inflammation (G0-4) were assessed using the Scheuer scoring system. The independent risk factors associated with SHD (≥G2/S2) were identified using univariable and multivariable logistic regression analyses, and a new scoring system based on these factors was established. Among the 883 enrolled patients, 548 (62.1 %) were male, and 250 (28.5 %) presented with SHD. ALT, platelet count, HBV DNA, and liver stiffness measurement were identified as independent risk factors. A new scoring model based on these factors, named APLB, was developed. The area under the curve of APLB was 0.731 (95 % confidence interval, 0.695–0.764), which was significantly higher than those of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. An APLB score <6 points ruled out SHD with 80.2 % sensitivity, while scores >12 points diagnosed SHD with 97.5 % specificity. In conclusion, the APLB scoring model demonstrated superior diagnostic performance compared with the APRI and the FIB-4 index, and it has the potential to guide the decision to initiate antiviral therapy in this patient group.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106234"},"PeriodicalIF":4.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572844","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}