Retinoic acid is a translation inhibitor against chikungunya virus both <i>in vitro</i> and <i>in vivo</i>

Yibo Chen; Zhiwei He; Ke Zhang; Xijing Qian; Yangang Liu; Xu Zheng; Ping Zhao; Zhongtian Qi; Cuiling Ding

doi:10.1016/j.virs.2026.06.013

August 2026

. doi: 10.1016/j.virs.2026.06.013

Citation: Yibo Chen, Zhiwei He, Ke Zhang, Xijing Qian, Yangang Liu, Xu Zheng, Ping Zhao, Zhongtian Qi, Cuiling Ding. Retinoic acid is a translation inhibitor against chikungunya virus both in vitro and in vivo .VIROLOGICA SINICA, 2026, 41(4) : 766-778. http://dx.doi.org/10.1016/j.virs.2026.06.013

维甲酸是一种在体内外抑制基孔肯雅病毒翻译的抑制剂

陈奕孛 ^a,b ,
何志伟 ^a,b ,
张柯 ^c ,
钱汐晶 ^a,b ,
刘延刚 ^a,b ,
郑旭 ^a,b ,
赵平 ^a,b ,
戚中田 ^a,b,, ,
丁翠玲 ^a,b,,

a 海军军医大学海军医学系生物医学防护教研室;
b 上海市生物医学防护重点实验室;
c 独立研究者

通讯作者： 戚中田, qizt@smmu.edu.cn; 丁翠玲, cuilingding@163.com
收稿日期： 2026-03-03
录用日期： 2026-06-29

摘要

基孔肯雅病毒（chikungunya virus, CHIKV）是一种经蚊媒传播的甲病毒，可引发致残性的发热及关节炎性疾病，长期以来对热带和亚热带地区的公共卫生构成持续威胁。目前尚无临床批准的抗病毒药物，这凸显了开发靶向性、高效治疗干预措施的迫切需求。通过对美国食品药品监督管理局（FDA）批准的小分子化合物库进行高通量筛选，本研究发现视黄酸（retinoic acid, RA）可作为多种虫媒病毒的广谱抑制剂，并对CHIKV表现出强效抑制活性。为明确RA抑制病毒的具体生命周期阶段，本研究开展了药物添加时间窗实验，并检测了RA对病毒吸附、内吞、膜融合、复制及翻译等环节的影响。值得注意的是，通过有限蛋白酶解-质谱联用技术发现，RA通过选择性靶向真核翻译起始因子4B（eukaryotic translation initiation factor 4B, EIF4B），从而干扰病毒翻译过程，发挥抗CHIKV作用。在CHIKV诱导的小鼠脑炎模型中，RA治疗性给药可显著减轻脑组织病理损伤、改善临床症状并提高生存率。在CHIKV诱导的小鼠关节炎模型中，RA治疗同样显著缓解足垫肿胀及病理改变。综上，本研究结果揭示了RA作为靶向EIF4B的抗CHIKV候选药物的潜力，为其进一步开发为CHIKV感染的治疗药物提供了实验依据。
- 基孔肯雅病毒
- , 虫媒病毒
- , 抗病毒药物
- , 维甲酸
- , 病毒翻译

Retinoic acid is a translation inhibitor against chikungunya virus both in vitro and in vivo

Yibo Chen ^a,b ,
Zhiwei He ^a,b ,
Ke Zhang ^c ,
Xijing Qian ^a,b ,
Yangang Liu ^a,b ,
Xu Zheng ^a,b ,
Ping Zhao ^a,b ,
Zhongtian Qi ^a,b,, ,
Cuiling Ding ^a,b,,

a. Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China;
b. Shanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China;
c. Independent Researcher, Shanghai, 200433, China

Corresponding author: Zhongtian Qi, qizt@smmu.edu.cn Cuiling Ding, cuilingding@163.com
Received Date: 03 March 2026
Accepted Date: 29 June 2026

Abstract

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 in vivo. 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.
- Chikungunya virus (CHIKV)
- , Arboviruses
- , Antiviral drug
- , Retinoic acid
- , Viral translation

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Electronic Supplementary Material

10.1016j.virs.2026.06.013-ESM.docx