Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus

Cheng Peng; Jialing Hu; Yuan Bai; Wei Wu; Wenting Mao; Yang Liu; Yi Wan; Lei Zhang; Wei Li; Tingting Tian; Tiezhu Liu; Yanhai Wang; Mifang Liang; Jun Han; Zhiming Yuan; Jiandong Li; Chao Shan; Fei Deng; Wei Wang

doi:10.1016/j.virs.2025.04.003

June 2025

. doi: 10.1016/j.virs.2025.04.003

Citation: Cheng Peng, Jialing Hu, Yuan Bai, Wei Wu, Wenting Mao, Yang Liu, Yi Wan, Lei Zhang, Wei Li, Tingting Tian, Tiezhu Liu, Yanhai Wang, Mifang Liang, Jun Han, Zhiming Yuan, Jiandong Li, Chao Shan, Fei Deng, Wei Wang. Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus .VIROLOGICA SINICA, 2025, 40(3) : 491-494. http://dx.doi.org/10.1016/j.virs.2025.04.003

利巴韦林与沙粒病毒进入抑制剂LHF-535联用显著增强对拉沙活病毒的抗病毒效果

彭诚 ^a ,
胡笳泠 ^a ,
白源 ^a,b ,
芜为 ^c ,
毛文婷 ^a,b ,
刘洋 ^a ,
万仪 ^a,b ,
张磊 ^a ,
李伟 ^d ,
田婷婷 ^c ,
刘铁柱 ^c ,
王衍海 ^c ,
梁米芳 ^c ,
韩俊 ^c ,
袁志明 ^a,b ,
李建东 ^c,, ,
单超 ^a,b,, ,
邓菲 ^a,b,, ,
王薇 ^a,b,,

a. 中国科学院武汉病毒研究所;
b. 中国科学院大学;
c. 中国疾病预防控制中心病毒病预防控制所;
d. 四川省疾病预防控制中心

通讯作者： 李建东, lijd@ivdc.chinacdc.cn; 单超, shanchao@wh.iov.cn; 邓菲, df@wh.iov.cn; 王薇, wangwei@wh.iov.cn
收稿日期： 2025-02-17
录用日期： 2025-04-07

摘要

拉沙病毒 (Lassa virus, LASV) 属沙粒病毒科 (Arenaviridae)、哺乳类沙粒病毒属 (Mammarenavirus), 于1969年在尼日尼亚被发现，是生物安全等级四级病原。LASV引起急性传染性出血热疾病拉沙热 (Lassa fever), 被世界卫生组织列为优先关注的新发传染病，在西非地区呈现地方性流行，年发病率超过30万例，重症率可达20%，对人类健康构成严重威胁，但目前尚无特效药物和疫苗。2024年8月，四川省报告了我国首例拉沙热输入病例，患者是一位从非洲几内亚归国人员，经核酸检测和全基因组测序确诊为拉沙热。在本项研究中，我们利用获得的临床样本，在生物安全四级（BSL-4）实验室，成功分离获得一株LASV临床分离株。通过透射电镜观察、全基因组测序技术以及免疫荧光抗原检测三联验证法，证实该毒株具备典型的沙粒病毒形态特征，其基因组结构与GPC基因编码区与Ⅳ型进化支参考毒株高度同源。为探索新型治疗策略，我们评估了核苷类似物利巴韦林（Ribavirin，广谱抗病毒药物）与新型病毒进入抑制剂LHF-535的联合抗病毒效应，结果显示，两药联用呈现显著协同抑制效应。该研究为开发针对LASV感染的新型治疗策略提供了关键依据，并凸显了联合用药策略在应对病毒耐药性方面的优势，具有重要的公共卫生防控意义。
- 拉沙病毒
- , 利巴韦林
- , LHF-535
- , 药物联用
- , 抗病毒效果

Coadministration of ribavirin and arenaviral entry inhibitor LHF-535 enhances antiviral benefit against authentic lassa virus

Cheng Peng ^a ,
Jialing Hu ^a ,
Yuan Bai ^a,b ,
Wei Wu ^c ,
Wenting Mao ^a,b ,
Yang Liu ^a ,
Yi Wan ^a,b ,
Lei Zhang ^a ,
Wei Li ^d ,
Tingting Tian ^c ,
Tiezhu Liu ^c ,
Yanhai Wang ^c ,
Mifang Liang ^c ,
Jun Han ^c ,
Zhiming Yuan ^a,b ,
Jiandong Li ^c,, ,
Chao Shan ^a,b,, ,
Fei Deng ^a,b,, ,
Wei Wang ^a,b,,

a. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China;
b. University of the Chinese Academy of Sciences, Beijing, 100049, China;
c. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, National Health Commission Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;
d. Center for Disease Control and Prevention of Sichuan Province, Chengdu, 610041, China

Corresponding author: Jiandong Li, lijd@ivdc.chinacdc.cn Chao Shan, shanchao@wh.iov.cn Fei Deng, df@wh.iov.cn Wei Wang, wangwei@wh.iov.cn
Received Date: 17 February 2025
Accepted Date: 07 April 2025

Abstract

Highlights
1. A new strain of Lassa virus (LASV) was successfully isolated and characterized.
2. The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV.
3. The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever.

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Electronic Supplementary Material

10.1016j.virs.2025.04.003-ESM.docx