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

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

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
Available online: 02 July 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

Electronic Supplementary Material

10.1016j.virs.2026.06.013-ESM.docx
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