Emerging Microbes & Infections最新文献

{"title":"Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFNα treated patients of chronic hepatitis B.","authors":"Bei Jiang, Guiwen Guan, Kaitao Zhao, Zhiqiang Gu, Lin Wang, Weilin Gu, Minghui Li, Yuchen Xia, Xiangmei Chen, Yifei Guo, Jiming Zhang, Zhenhuan Cao, Man-Fung Yuen, Fengmin Lu","doi":"10.1080/22221751.2025.2475847","DOIUrl":"10.1080/22221751.2025.2475847","url":null,"abstract":"<p><strong>Background & aims: </strong>A notable proportion of CHB patients undergoing PEG-IFNα based therapy experience lagged serum HBeAg and/or HBV DNA disappearance in patients achieving HBsAg loss. In this study, we explored the molecular mechanisms behind this clinical phenomenon, offering novel insights into the sustainability of chronic HBV infection.</p><p><strong>Methods: </strong>Two independent clinical cohorts were enrolled to validate this phenomenon. Then comprehensive analysis was performed using public datasets, coupled with a series of molecular biology experiments.</p><p><strong>Results: </strong>Approximately 17-20% CHB patients underwent PEG-IFNα based therapy experienced seroclearance of HBsAg, while serum HBeAg and/or HBV DNA remained positive. These patients are more prone to serum HBsAg reappearance compared to those achieving complete virological response. Analysis of public datasets revealed that compared to the PC/BCP, the SP1/SP2 promoter displayed more pronounced inhibitory epigenetic modifications in HBeAg-negative patients and SP1/SP2 in-frame mutation peaked in immune active patients. <i>In vitro</i> experiments demonstrated that introduced SP1/SP2 inactive mutations would enhance PC/BCP transcriptional activity by a mechanism known as adjacent transcriptional interference. Furthermore, the deletion of L-HBsAg facilitated intracellular cccDNA replenishment.</p><p><strong>Conclusion: </strong>This study elucidates that under IFNα treatment and low viral load, transcriptional suppression of SP1/SP2 promoters through mutations and/or epigenetic changes would favour the maintenance of sustain chronic HBV infection, via enhancing the transcription activity of BCP to promote cccDNA replenishment.</p><p><strong>Impact and implications: </strong>In clinical practice with IFNα antiviral treatment for CHB patients, a \"paradoxical\" phenomenon is observed where serum HBsAg disappears while HBV DNA or/and HBeAg remains at low positive levels, with delayed disappearance. Our study confirms this clinical phenomenon using two independent clinical cohorts and explores the potential mechanisms behind the persistence of chronic HBV infection under IFNα treatment and low viral load. Transcriptional suppression of SP1/SP2 promoters through mutations and/or epigenetic changes supports the maintenance of chronic HBV infection by enhancing the transcriptional activity of the BCP, which in turn promotes cccDNA replenishment.</p><p><p>HighlightsApproximately 20% of patients with CHB who have just achieved HBsAg loss under IFNα treatment show positive serum HBV DNA and/or HBeAg.During disease progression, in frame indel mutations accumulate in the HBV genome's SP1 and SP2 promoters, with epigenetic modifications contributing to their suppression.In frame indel mutations in the HBV genome's SP1 and SP2 promoters inhibit the transcription of HBV S mRNA and promote the transcription of 3.5 kb HBV RNA.The loss of L-HBs and envelop proteins lead","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2475847"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing of peripheral blood mononuclear cells reveals immune landscape of monkeypox patients with HIV.","authors":"Yamin Liu, Xinhua Liu, Jingjing Wang, Ying Xie, Jing Guo, Zhiqiang Liu, Ying Li, Bei Jiang, Jingya Wang","doi":"10.1080/22221751.2025.2459136","DOIUrl":"10.1080/22221751.2025.2459136","url":null,"abstract":"<p><p>The monkeypox (MPXV) outbreak in 2022 is more prevalent among individuals with human immunodeficiency virus (HIV). While it is plausible that HIV-induced immunosuppression could result in a more severe progression, the exact mechanisms remain undetermined. To better understand the immunopathology of MPXV in patients with and without HIV infection, we employed single-cell RNA sequencing (scRNA-seq) to analyse peripheral blood mononuclear cells (PBMCs) from six patients hospitalized for MPXV, three of whom had HIV infection (HIV antibody positive and HIV RNA level below the detection limit), and three patients only infected with MPXV (HIV-). We map the peripheral immune response in both the acute phase and the recovery period, showing the reconfiguration of peripheral immune cell phenotypes in acute stage compared with recovery stage, characterized by disturbed cell subsets and intense cell interactions mediated by monocytes and neutrophils. Importantly, we also found obviously dysregulated gene expression and cell subsets in HIV+ patients proposing mechanism underlying their serious condition. Our findings provide a comprehensive cell atlas of MPXV patients, shed light on the mechanisms underlying the severe disease progression and longer recovery time in HIV+ individuals.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2459136"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of a predictive model for meningoencephalitis in pediatric scrub typhus based on machine learning algorithms.","authors":"Yonghan Luo, Wenrui Ding, Xiaotao Yang, Houxi Bai, Feng Jiao, Yan Guo, Ting Zhang, Xiu Zou, Yanchun Wang","doi":"10.1080/22221751.2025.2469651","DOIUrl":"10.1080/22221751.2025.2469651","url":null,"abstract":"<p><p>To retrospectively analyze the clinical characteristics of pediatric scrub typhus (ST) with meningoencephalitis (STME) and to construct and validate predictive models using machine learning.Clinical data were collected from 100 cases of pediatric STME and matched with data from 100 ST cases without meningitis using propensity-score matching. Risk factors for STME in pediatrics were identified through the least absolute shrinkage and selection operator (LASSO) regression analysis. Six predictive models-Logistic Regression, K-Nearest Neighbors, Naive Bayes, Multi-layer Perceptron(MLP), Random Forest, and XGBoost-were constructed using the training set and evaluated for performance, with validation conducted on the test set. The Shapley Additive Explanations (SHAP) method was applied to rank the importance of each variable.All children improved and were discharged following treatment with azithromycin/doxycycline (1/99). Twelve variable features were identified through the LASSO regression. Of the six predictive models developed, the XGBoost model demonstrated the highest performance in the training set (AUC = 0.926), though its performance in the test set was moderate (AUC = 0.740). The MLP model exhibited robust predictive performance in both training and test sets, with AUCs of 0.897 and 0.817, respectively. Clinical decision curve analysis indicated that the MLP and XGBoost models provide significant clinical utility. SHAP analysis identified the most important predictors for STME as ferritin, white blood cell count, edema, prothrombin time, fibrinogen, duration of pre-admission fever, eschar, activated partial thromboplastin time, splenomegaly, and headache. The MLP and XGBoost models showed strong predictive capability for pediatric STME, with favorable outcomes following doxycycline-based therapy.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2469651"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV molecular transmission networks among students in Guangxi: unraveling the dynamics of student-driven HIV epidemic.","authors":"Xianwu Pang, Jie Ma, Qin He, Kailing Tang, Jinghua Huang, Ningye Fang, Haomin Xie, Guanghua Lan, Shujia Liang","doi":"10.1080/22221751.2025.2459142","DOIUrl":"10.1080/22221751.2025.2459142","url":null,"abstract":"<p><p>In Guangxi, the number of newly diagnosed HIV-1 infections among students is continuously increasing, highlighting the need for a detailed understanding of local transmission dynamics, particularly focusing on key drivers of transmission. We recruited individuals newly diagnosed with HIV-1 in Nanning, Guangxi, and amplified and sequenced the HIV-1 pol gene to construct a molecular network. Bayesian phylogenetic analysis was utilized to identify migration events, and multivariable logistic regression was employed to analyze factors influencing clustering and high linkage. The predominant subtype among students was CRF07_BC (58.5%), followed by CRF01_AE (17.4%) and CRF55_01B (13.5%). Transmission network analysis identified a significant clustering rate of 64.3% among students, primarily within large clusters. The strongest transmission relationships were observed between students and MSM aged 25-39, as well as nonstudent youths. These migration events primarily occurred from MSM aged 25-39 to students and nonstudent youths for CRF01_AE, CRF07_BC, and CRF55_01B. Qingxiu was the main emigration region for for CRF01_AE, CRF07_BC, while Xixiangtang for CRF55_01B. Link with nonstudent youths (AOR = 5.11) and MSM aged 25-39 (AOR = 8.82) were significant factors contributing to the high linkage among students. Long-term infection was a key factor in super spreaders. These findings emphasize the critical role of MSM aged 25-39 in HIV-1 transmission among local youths, particularly regarding long-term infected individuals. The study advocates for targeted HIV-1 screening and intervention strategies for youths to strengthen early detection and treatment, thereby mitigating further transmission within this high-risk group.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2459142"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the epidemiology of <i>Mycoplasma pneumoniae</i> infections in China in 2022-2024: a nationwide cross-sectional study of over 1.6 million cases.","authors":"Yamin Sun, Pei Li, Ronghua Jin, Yaoming Liang, Jiale Yuan, Zhongxin Lu, Junrong Liang, Yingmiao Zhang, Hongyu Ren, Yuanyuan Zhang, Jianchun Chen, Yun Huang, Chuixu Lin, Yinghua Li, Jianfeng Zhou, Xi Wang, You Li, Senzhong Huang, Jianguo Xu, Tian Qin","doi":"10.1080/22221751.2025.2482703","DOIUrl":"10.1080/22221751.2025.2482703","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i> (MP) is a leading cause of community-acquired pneumonia (CAP), accounting for 10-40% of cases in children. In China, the high prevalence of macrolide-resistant MP (MRMP) and recurrent MP epidemics place a significant burden on the healthcare system. Leveraging data from over 1.6 million cases, this study provides a comprehensive analysis of the epidemiological characteristics of MP across China. Seasonal patterns analysis revealed three distinct transmission zones in China. Transmission Zone 1 exhibited two annual epidemic peaks, while Zones 2 and 3 showed a single annual peak of distinct timings. Notably, winter travel to popular tourist destinations appears to influence MP infection patterns in China. Age- and sex- specific analysis indicated male newborns aged [0-1) years face a 1.67 times higher risk of MP infection compared to females. Conversely, females aged [23-38) years have a higher infection risk, likely due to their caregiving roles. The proportion of MRMP surged from 80.00% to 93.02% between July 2023 and May 2024, with a median growth rate of 10.21%. This rapid increase contrasts sharply with the modest 5.3% rise observed from 2011 to 2019, and we attribute this escalation in part to the growing prevalence of the T1-3R clade strain in China. These findings have important implications for the identification of high-risk population, place, and time for more targeted efforts of prevention and treatment. Furthermore, the rapidly increased proportion of MRMP in the 2023-2024 season raises a concerning signal regarding antibiotic use.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2482703"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal seroprevalence of Crimean-Congo hemorrhagic fever virus in Southern Uganda.","authors":"Evan A Mihalakakos, Victor Ssempijja, Ruy M Ribeiro, Carmen Molina-Paris, Gerald Katushabe, Josephine Nalwadda, Jonah Omooja, Denis K Byarugaba, Kyle Rosenke, Steven J Reynolds, Mary K Grabowski, Ronald M Galiwango, Robert Ssekubugu, Heinz Feldmann, David W Hawman","doi":"10.1080/22221751.2025.2465315","DOIUrl":"10.1080/22221751.2025.2465315","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease endemic to many regions of Africa, the Middle East, Southeast Asia and the Balkans. Caused by the CCHF virus (CCHFV), CCHF has been a recognized cause of illness in Uganda since the 1950s and recently, more intensive surveillance suggests CCHFV is widely endemic within the country. Most surveillance has been focused on the Ugandan cattle corridor due to the risk of CCHFV exposure associated with livestock practices. Here we evaluated the seroprevalence of CCHFV in several Southern Ugandan communities outside the cattle corridor combined with longitudinal sample sets to measure the immune response to CCHFV for up to a decade. Interestingly, across three community types, agrarian, trading and fishing, we detected CCHFV seroprevalence in all three but found the highest seroprevalence in fishing communities. We also measured consistent CCHFV-specific antibody responses for up to a decade. Our findings support the conclusion that CCHFV is widely endemic in Uganda and highlight that additional communities may be at risk for CCHFV exposure.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2465315"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses.","authors":"Chloe Qingzhou Huang, Rory A Hills, George W Carnell, Sneha Vishwanath, Ernest T Aguinam, Andrew C Y Chan, Phil Palmer, Laura O'Reilly, Paul Tonks, Nigel Temperton, Simon D W Frost, Laurence S Tiley, Mark R Howarth, Jonathan L Heeney","doi":"10.1080/22221751.2025.2511132","DOIUrl":"10.1080/22221751.2025.2511132","url":null,"abstract":"<p><p>The increasing spread of highly pathogenic avian influenza (HPAI) A/H5 viruses poses a pandemic threat. Circulating clade 2.3.4.4b viruses have demonstrated rapid transcontinental dissemination, extensive reassortment, epizootic spread and potential sustained mammal-to-mammal transmission, signifying a heightened risk of becoming a human pathogen of high consequence. A broadly protective, future-proof vaccine against multiple clades of H5 influenza is urgently needed for pandemic preparedness. Here, we combine two novel vaccine technologies to generate a Digitally Immune Optimised and Selected H5 antigen (DIOSvax-H5_inter) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunized with DIOSvax-H5_inter Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralizing antibody and T cell responses against diverse H5 strains. DIOSvax-H5_inter Homotypic Nanocages provide a scalable vaccine candidate with the potential for pan-H5 protection against drifted or newly emergent H5 strains. This World Health Organization preferred characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2511132"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza vaccine effectiveness among primary and secondary school students in Shenzhen during the 2023/24 influenza season.","authors":"Yawen Jiang, Jiatong Sun, Fang Huang, Xu Xie, Xin Wang, Xiaoliang Wu, Min Jiang, Ying Sun, Hui Liu, Huiqiao Gu, Quan Lu, Xiaozhen Chen, Tiejian Feng, Shisong Fang, Jianhua Lu, Yuelong Shu","doi":"10.1080/22221751.2025.2490531","DOIUrl":"10.1080/22221751.2025.2490531","url":null,"abstract":"<p><p>During the winter influenza peaks, a total of 2689 ILI patients were collected from the two hospitals, with 58.61% of the participants vaccinated. Of the ILI patients, 761 (28.3%) were laboratory-confirmed influenza infection, with 76.7% being A(H3N2) and 22.8% B/Victoria. After adjusting for covariates, the adjusted VE (aVE) was 57.06% (95% CI, 48.59-64.13%). In the subtype/lineage and age subgroup analysis, influenza VE against B/Victoria was higher than A(H3N2), and decreased with age. More, influenza VE (aVE = 19.63% [95% CI, -29.13-49.98%]) against all subtypes/lineages were not statistically significant for the spring-summer peak. Overall, influenza vaccines provided significant protection against influenza-associated outpatient visits among students in Shenzhen during 2023/24 winter influenza season. The findings underscore the importance of maintaining high vaccination coverage.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2490531"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High HBsAg clearance rate and viral dynamics in HBeAg-positive, ALT-normal children and adolescents with chronic HBV infection: results from the prospective sprout project.","authors":"Xin Wang, Changxiang Lai, Ruiling Li, Jia Lei, Yuyin Xie, Zhiyu Li, Qiyuan Tang, Qing He, Hongfei Zhang, Zheng Zhang, Fang Wang","doi":"10.1080/22221751.2025.2516173","DOIUrl":"10.1080/22221751.2025.2516173","url":null,"abstract":"<p><p>Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection in children and adolescents with normal alanine aminotransferase (ALT) levels constitutes a substantial population in China, yet the optimal timing for antiviral therapy remains unclear. This prospective, real-world study, conducted as the primary centre of the Sprout Project, evaluated the hepatitis B surface antigen (HBsAg) loss rate and viral-immune dynamics of pegylated interferon α (PEG-IFN-α) treatment in 85 chronic HBV patients aged 3-18 years over a 24-month period. A total of 27 HBeAg-positive, ALT-normal patients were selected for analysis. Patients were treated with a combination of PEG-IFN-α and entecavir. After 24 months, the overall HBsAg loss rate was 48.15%, with 47.37% in the immune-tolerant phase and 50% in the grey zone phase. Among those who cleared HBsAg, 84.62% had ALT elevation prior to anti-HBsAg antibody (HBsAb) seroconversion, which occurred 28-400 days before HBsAg loss. While HBsAg and HBV DNA were cleared by 24 months in the HBsAg loss group, 23.08% of children remained HBeAg-positive. Notably, 61.54% developed detectable HBsAb prior to HBsAg loss. Children aged 3-7 years had significantly higher clearance rates than those aged 8-18 years. These findings support the effectiveness of PEG-IFN-α combined with nucleos(t)ide analogs in achieving high HBsAg loss rates in young, HBeAg-positive, ALT-normal chronic HBV children and adolescents, with immune activation potentially preceding ALT elevation, and offers valuable insights into the viral-immune dynamics during treatment, highlighting the potential of antiviral therapy in this population.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2516173"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorinated biscoumarins inhibit chikungunya virus replication in cell-based and animal models.","authors":"Chidinma Nelson Orji, Naphat Loeanurit, Van-Can Pham, Thi-Hong-Truc Phan, Kowit Hengphasatporn, Yasuteru Shigeta, Altri Diana Putri, Laura Sandra Lello, Andres Merits, Noppadol Wacharachaisurapol, Wanna Eiamart, Supeecha Wittayalertpanya, Tanatorn Khotavivattana, Warinthorn Chavasiri, Siwaporn Boonyasuppayakorn","doi":"10.1080/22221751.2025.2529889","DOIUrl":"10.1080/22221751.2025.2529889","url":null,"abstract":"<p><p>Biscoumarin derivatives were evaluated for antiviral activity against chikungunya virus (CHIKV), a re-emerging mosquito-borne alphavirus with no approved treatment. Compounds 3 and 4 demonstrated potent <i>in vitro</i> antiviral efficacy, with EC₅₀ values of 2.85 ± 0.42 µM and 3.08 ± 0.45 µM (SI > 20) for compound 3 in Vero and HEK293 cells, respectively. Compound 4 showed comparable potency in Vero cells but was less effective in HEK293 cells. Time-of-addition and replicon assays suggested that both compounds act at a post-entry step, likely inhibiting viral RNA replication. <i>In vivo</i>, a single oral dose of 250 mg/kg was well tolerated in mice and rats, with no signs of acute hepatorenal toxicity and favourable pharmacokinetic profiles. Compound 3 & 4 significantly reduced tissue viral loads within 24 hours; however, their antiviral effect diminished after the drug was cleared from circulation. Due to concerns about potential cumulative toxicity, repeated administration was avoided. Preliminary mechanistic studies indicated moderate inhibition of the viral nsP1 methyltransferase and suggested possible involvement of host pathways. These findings highlight biscoumarin derivatives - particularly compound 3 - as promising antiviral candidates against CHIKV, meriting further optimization and investigation into their mechanisms of action.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2529889"},"PeriodicalIF":7.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}