Virologica Sinica最新文献

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Effectiveness of lignans against severe fever with thrombocytopenia syndrome virus infection 木脂素对重症发热伴血小板减少综合征病毒感染的疗效。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-09 DOI: 10.1016/j.virs.2026.07.003
Jun Huang, Jinpeng Lv, Xiaojie Zheng, Junjun Jiang, Wei Liu, Shuchen Liu, Hao Liang, Hao Li
{"title":"Effectiveness of lignans against severe fever with thrombocytopenia syndrome virus infection","authors":"Jun Huang,&nbsp;Jinpeng Lv,&nbsp;Xiaojie Zheng,&nbsp;Junjun Jiang,&nbsp;Wei Liu,&nbsp;Shuchen Liu,&nbsp;Hao Liang,&nbsp;Hao Li","doi":"10.1016/j.virs.2026.07.003","DOIUrl":"10.1016/j.virs.2026.07.003","url":null,"abstract":"<div><div>Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes a life-threatening infectious disease with high mortality. Currently, there are no approved vaccines or specific therapeutic drugs for clinical use against SFTSV infection. Here, we screened a lignan compound library to identify candidates with anti-SFTSV activity. Two type I arylnaphthalide lignan lactones, Pronaphthalide A and Procumbenoside I, were identified as potent inhibitors of SFTSV infection. Mechanistic investigations indicated that these lignans exert their inhibitory effects at the viral binding and internalization stages. Molecular docking analysis revealed that these lignans can bind to the conserved B domain of the SFTSV glycoprotein Gn, an interaction validated by subsequent experiments as the core mechanism underlying their antiviral activity. In a mouse model of lethal SFTSV infection, treatment with these compounds, particularly Procumbenoside I, significantly inhibited viral infection, attenuated histopathological abnormalities, and improved survival rates. The antiviral activity of these lignans was further expanded to other bunyaviruses, including Lymphocytic choriomeningitis virus (LCMV) and Wetland virus (WELV). These findings uncover the broad-spectrum antiviral activity of type I arylnaphthalide lignans and support their potential as candidate therapeutic agents for the clinical intervention of bunyavirus infections.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 912-922"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stabilization of prefusion hMPV F improves manufacturability and protective immunity across hMPV lineages 预熔hMPV F的稳定性提高了hMPV谱系的可制造性和保护性免疫。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-08-06 DOI: 10.1016/j.virs.2026.08.002
Changbin Qu, Jingjing Zou, Dongyu Niu, Qingxin Wu, Lijie Liu, Mengting Yu, Qiqi Zhang, Long Zhang, Shuai Wei, Wei Zhang, Wei Peng
{"title":"Stabilization of prefusion hMPV F improves manufacturability and protective immunity across hMPV lineages","authors":"Changbin Qu,&nbsp;Jingjing Zou,&nbsp;Dongyu Niu,&nbsp;Qingxin Wu,&nbsp;Lijie Liu,&nbsp;Mengting Yu,&nbsp;Qiqi Zhang,&nbsp;Long Zhang,&nbsp;Shuai Wei,&nbsp;Wei Zhang,&nbsp;Wei Peng","doi":"10.1016/j.virs.2026.08.002","DOIUrl":"10.1016/j.virs.2026.08.002","url":null,"abstract":"<div><div>Human metapneumovirus (hMPV) is a major cause of pediatric acute lower respiratory tract infections (ALRTIs), yet vaccine development has been hindered by the intrinsic metastability of the prefusion F glycoprotein (pre-F). Here, we used a structure-based design strategy to stabilize hMPV pre-F while preserving neutralization-sensitive epitopes. By applying combined stabilizing elements, including disulfide bonds, a designed salt bridge, and a trimer-interface sequence swap, we generated VM-874, a pre-F-stabilized trimer that was expressed at high levels in 293F cells and exhibited improved thermal stability and stress-resistant antigenicity. VM-874 also retained binding to multiple conformation-sensitive monoclonal antibodies following thermal and storage stress. VM-874 elicited high serum neutralizing titers against both hMPV A2 and B1 strains and conferred protection in BALB/c mice and cotton rats, as evidenced by reduced pulmonary viral burden and attenuated lung pathology after challenge. Although VM-874 elicited antibodies that cross-bound respiratory syncytial virus (RSV) F protein, no RSV-neutralizing activity was detected, underscoring the need to distinguish cross-reactivity from heterologous protection in combined RSV/hMPV vaccine strategies.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 947-960"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Y-box-binding protein 1 stabilizes the capsid protein of porcine circovirus type 2 to promote viral replication y -box结合蛋白1稳定猪圆环病毒2型衣壳蛋白,促进病毒复制。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-08-12 DOI: 10.1016/j.virs.2026.08.008
Jianwei Zhou, Qianqian Zhang, Xue Dong, Wei Gao, Xiaoyuan Lan, Beiyi Zhou, Yonghui Qiu, Weiyin Xu, Peng Hui, Penghui Zeng, Dedong Wang, Lei Hou, Jue Liu
{"title":"Y-box-binding protein 1 stabilizes the capsid protein of porcine circovirus type 2 to promote viral replication","authors":"Jianwei Zhou,&nbsp;Qianqian Zhang,&nbsp;Xue Dong,&nbsp;Wei Gao,&nbsp;Xiaoyuan Lan,&nbsp;Beiyi Zhou,&nbsp;Yonghui Qiu,&nbsp;Weiyin Xu,&nbsp;Peng Hui,&nbsp;Penghui Zeng,&nbsp;Dedong Wang,&nbsp;Lei Hou,&nbsp;Jue Liu","doi":"10.1016/j.virs.2026.08.008","DOIUrl":"10.1016/j.virs.2026.08.008","url":null,"abstract":"<div><div>Porcine circovirus type 2 (PCV2), a major causative agent of PCV2-associated diseases, poses a serious threat to the global swine industry. The stability of PCV2 capsid (Cap) protein is critical for viral replication; however, the underlying mechanisms regulating Cap stability during PCV2 infection remain poorly understood. In this study, co-immunoprecipitation assays were used to demonstrate that PCV2 Cap protein can maintain its own stability by binding to the cellular Y-box-binding protein 1 (YBX1) during viral infection. Furthermore, binding domain mapping experiments revealed two specific regions essential for this interaction: the N-terminal arginine-rich motif (ARM) of PCV2 Cap (amino acid sequence: <sup>1</sup>MTYPRRRYRRRRHRPRSHLG<sup>20</sup>) and the amino acid residues <sup>189</sup>RRRR<sup>192</sup> within the C-terminal domain (CTD) of YBX1. Virus rescue experiments further confirmed that substituting all arginine residues with alanine in the N-terminal ARM of Cap completely abolished its binding to YBX1. Analysis of viral replication capacity showed that YBX1 promotes PCV2 replication by stabilizing the viral Cap protein. Additionally, knockdown of <em>YBX1</em> significantly reduced the protein levels of PCV2 Cap, and this effect was reversed either by treatment with the proteasome inhibitor MG132 or by restoring YBX1 expression. Collectively, these findings demonstrate that YBX1 promotes PCV2 replication by directly interacting with the ARM of PCV2 Cap, thereby inhibiting the proteasomal degradation of Cap during viral infection.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 868-881"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication 宿主OTUB2和病毒plpro稳定NSP8促进SARS-CoV-2复制
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-27 DOI: 10.1016/j.virs.2026.07.008
Wenying Gao, Hongfei Wang, Jingguo Xin, Chenjia Gu, Lu Qiu, Xue Zhang, Chunlei Wang, Qingxiang Zhang, Shuai Li, Guangquan Li, Wenyan Zhang
{"title":"Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication","authors":"Wenying Gao,&nbsp;Hongfei Wang,&nbsp;Jingguo Xin,&nbsp;Chenjia Gu,&nbsp;Lu Qiu,&nbsp;Xue Zhang,&nbsp;Chunlei Wang,&nbsp;Qingxiang Zhang,&nbsp;Shuai Li,&nbsp;Guangquan Li,&nbsp;Wenyan Zhang","doi":"10.1016/j.virs.2026.07.008","DOIUrl":"10.1016/j.virs.2026.07.008","url":null,"abstract":"<div><div>The ubiquitin-proteasome system (UPS) plays a central role in antiviral defense but is also frequently hijacked by viruses to facilitate their replication. Here, we demonstrate that the host deubiquitinase OTUB2 stabilizes the viral replication factor NSP8 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through a dual-track mechanism. OTUB2 directly removes polyubiquitin chains from NSP8 to prevent its degradation. In parallel, OTUB2 stabilizes the viral papain-like protease (PLpro), which further promotes NSP8 stability through deubiquitination. Together, these effects preserve the functional integrity of the viral replication-transcription complex. Mechanistically, OTUB2-mediated stabilization of NSP8 potentiates NSP8-dependent suppression of type I interferon signaling, thereby promoting viral replication and immune evasion. Importantly, inhibition of OTUB2 disrupts OTUB2-mediated stabilization of NSP8 and PLpro, resulting in a marked reduction in viral replication and disease severity in cell culture systems and a hamster infection model. Collectively, our findings reveal a previously unrecognized mechanism by which SARS-CoV-2 utilizes the host deubiquitination system to stabilize its replication machinery and identify OTUB2 as a potential target for host-directed antiviral intervention.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 806-819"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Viral kinetics of the Chikungunya virus ESCA-MAL lineage during the 2025 Guangdong outbreak 基孔肯雅病毒ESCA-MAL谱系在2025年广东暴发期间的病毒动力学
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-06-09 DOI: 10.1016/j.virs.2026.06.004
Yuwei He, Chuting Zeng, Shuyan Tan, Xin Zhang, Silin Xiang, Chumin Liang, Shanshan Gao, Baisheng Li, Jing Lu
{"title":"Viral kinetics of the Chikungunya virus ESCA-MAL lineage during the 2025 Guangdong outbreak","authors":"Yuwei He,&nbsp;Chuting Zeng,&nbsp;Shuyan Tan,&nbsp;Xin Zhang,&nbsp;Silin Xiang,&nbsp;Chumin Liang,&nbsp;Shanshan Gao,&nbsp;Baisheng Li,&nbsp;Jing Lu","doi":"10.1016/j.virs.2026.06.004","DOIUrl":"10.1016/j.virs.2026.06.004","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 988-992"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pre-existing hemagglutinin-specific antibody levels are associated with B-cell repertoire maturation and antibody breadth after influenza vaccination 流感疫苗接种后,预先存在的血凝素特异性抗体水平与b细胞库成熟和抗体广度相关。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-08-10 DOI: 10.1016/j.virs.2026.08.007
Wei Wang, Yan Sun, Qing Liu, Yidan Xia, Jing Wang, Minhao Hu, Mengyao Kong, Jun He, Rongbao Gao, Yong Gao
{"title":"Pre-existing hemagglutinin-specific antibody levels are associated with B-cell repertoire maturation and antibody breadth after influenza vaccination","authors":"Wei Wang,&nbsp;Yan Sun,&nbsp;Qing Liu,&nbsp;Yidan Xia,&nbsp;Jing Wang,&nbsp;Minhao Hu,&nbsp;Mengyao Kong,&nbsp;Jun He,&nbsp;Rongbao Gao,&nbsp;Yong Gao","doi":"10.1016/j.virs.2026.08.007","DOIUrl":"10.1016/j.virs.2026.08.007","url":null,"abstract":"<div><div>Repeated influenza exposures generate complex antibody landscapes, yet how pre-existing antibodies are associated with subsequent vaccine responses remains unclear. We longitudinally tracked 21 adults stratified by pre-vaccination neutralizing titers to examine B-cell dynamics using flow cytometry, B cell receptor (BCR) sequencing, and monoclonal antibody characterization. After vaccination, participants with high baseline titers showed a longitudinal increase in the frequency of HA<sup>+</sup>CD27<sup>−</sup>IgD<sup>+</sup> naive-phenotype B cells. BCRs recovered from hemagglutinin (HA)-binding (HA<sup>+</sup>) B cells in the high-titer group displayed lower somatic hypermutation and shorter CDR3s, whereas those recovered from the lower-titer groups showed higher mutation levels and more extensive class switching. Correspondingly, monoclonal antibodies from the high-titer group generally showed narrow reactivity, while those from lower-titer groups showed broader neutralizing activity against historical strains. Clonal tracing further suggested that mAbs from lower-titer groups were more often linked to pre-existing sequences. Together, these findings suggest that pre-existing antibody levels are associated with differences in B-cell repertoire maturation and antibody breadth after influenza vaccination.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 898-911"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy 由NS1反式互补产生的复制缺陷蜱传脑炎病毒具有强大的保护作用。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-30 DOI: 10.1016/j.virs.2026.07.010
Ji Zhang, Qiu-Yan Zhang, Zhe-Rui Zhang, Ya-Nan Zhang, Hong-Qing Zhang, Cheng-Lin Deng, Bo Zhang
{"title":"A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy","authors":"Ji Zhang,&nbsp;Qiu-Yan Zhang,&nbsp;Zhe-Rui Zhang,&nbsp;Ya-Nan Zhang,&nbsp;Hong-Qing Zhang,&nbsp;Cheng-Lin Deng,&nbsp;Bo Zhang","doi":"10.1016/j.virs.2026.07.010","DOIUrl":"10.1016/j.virs.2026.07.010","url":null,"abstract":"<div><div>Tick-borne encephalitis virus (TBEV) poses a severe threat to public health, causing neurological disorders with high morbidity and mortality in endemic regions. Therefore, developing safe and effective strategies for TBEV vaccines has long been a focus of attention. Herein, leveraging our well-established NS1 <em>trans</em>-complementation platform, we successfully constructed a high-titer replication-defective TBEV (TBEV-ΔNS1) using the BHK-21 cell line stably expressing Omsk hemorrhagic fever virus (OHFV) NS1 (designated BHK<sub>NS1</sub>). Retention of the NS1 deletion in TBEV-ΔNS1 was confirmed by continuous passaging in BHK<sub>NS1</sub> cells, as no replicative virus was detected in naive BHK-21 cells. The safety profile of TBEV-ΔNS1 was further validated, as administration of a high dose of TBEV-ΔNS1 to ICR mice did not induce any clinical symptoms. Notably, TBEV-ΔNS1 conferred complete protection against lethal wild-type (WT) TBEV challenge in ICR mice, whereas non-immunized control mice exhibited 100% mortality, significant weight loss, and viremia. This protective efficacy is tightly correlated with robust humoral and cellular immune responses, as demonstrated by the induction of high titers of TBEV-specific IgG, neutralizing antibodies, and IFN-γ-secreting CD8<sup>+</sup> T cells following a single immunization. Collectively, our findings provide a proof-of-concept for the NS1 <em>trans</em>-complementation platform in TBEV vaccine development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 937-946"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hidden diversity of coronaviruses in high-altitude plateau mammals 高原哺乳动物冠状病毒隐藏的多样性
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-15 DOI: 10.1016/j.virs.2026.07.004
Lin Xu, Edward C. Holmes, Weifeng Shi
{"title":"Hidden diversity of coronaviruses in high-altitude plateau mammals","authors":"Lin Xu,&nbsp;Edward C. Holmes,&nbsp;Weifeng Shi","doi":"10.1016/j.virs.2026.07.004","DOIUrl":"10.1016/j.virs.2026.07.004","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 1002-1005"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Whole-genome evolutionary dynamics of human parainfluenza virus type 3 in Shanghai, China, 2016–2024 2016-2024年上海市人副流感病毒3型全基因组进化动态
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-14 DOI: 10.1016/j.virs.2026.07.005
Yuqing Zhou, Xiao Wang, Lu Zhang, Yang Yuan, Tianchun Liu, Yuqin Yang, Yingjie Zheng, Bing Zhao
{"title":"Whole-genome evolutionary dynamics of human parainfluenza virus type 3 in Shanghai, China, 2016–2024","authors":"Yuqing Zhou,&nbsp;Xiao Wang,&nbsp;Lu Zhang,&nbsp;Yang Yuan,&nbsp;Tianchun Liu,&nbsp;Yuqin Yang,&nbsp;Yingjie Zheng,&nbsp;Bing Zhao","doi":"10.1016/j.virs.2026.07.005","DOIUrl":"10.1016/j.virs.2026.07.005","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 993-998"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retinoic acid is a translation inhibitor against chikungunya virus both in vitro and in vivo 维甲酸是基孔肯雅病毒在体内和体外的翻译抑制剂。
IF 4.7 3区 医学
Virologica Sinica Pub Date : 2026-08-01 Epub Date: 2026-07-02 DOI: 10.1016/j.virs.2026.06.013
Yibo Chen, Zhiwei He, Ke Zhang, Xijing Qian, Yangang Liu, Xu Zheng, Ping Zhao, Zhongtian Qi, Cuiling Ding
{"title":"Retinoic acid is a translation inhibitor against chikungunya virus both in vitro and in vivo","authors":"Yibo Chen,&nbsp;Zhiwei He,&nbsp;Ke Zhang,&nbsp;Xijing Qian,&nbsp;Yangang Liu,&nbsp;Xu Zheng,&nbsp;Ping Zhao,&nbsp;Zhongtian Qi,&nbsp;Cuiling Ding","doi":"10.1016/j.virs.2026.06.013","DOIUrl":"10.1016/j.virs.2026.06.013","url":null,"abstract":"<div><div>Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes debilitating febrile and arthritic disease and remains a persistent public health threat in tropical and subtropical regions, with no clinically approved antiviral drugs currently available, which underscores the urgent need for targeted and effective therapeutic interventions. Through high-throughput screening of an FDA-approved compound library, we identified retinoic acid (RA) as a broad-spectrum inhibitor of multiple arboviruses, exhibiting potent activity against CHIKV. Time-of-addition experiments, together with assays on viral binding, endocytosis, membrane fusion, replication and translation, were performed to determine the specific lifecycle stages inhibited by RA. Notably, RA exerts anti-CHIKV effects by selectively targeting eukaryotic translation initiation factor 4B (EIF4B), thereby disrupting the viral translation, as revealed by limited proteolysis-mass spectrometry (LiP-MS). And, our results demonstrated that RA administration exerted potent protective effects against CHIKV infection <em>in vivo</em>. Specifically, RA significantly reduced cerebral pathological damage, relieved clinical manifestations, and enhanced survival in a murine model of CHIKV-induced encephalitis, while also markedly attenuating footpad swelling and joint pathological alterations in a CHIKV-induced arthritis mouse model. Collectively, our findings highlight RA as a promising anti-CHIKV candidate targeting EIF4B, supporting its further development as a therapeutic agent against CHIKV infection.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"41 4","pages":"Pages 766-778"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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