Rifapentine is an entry and replication inhibitor against yellow fever virus both in vitro and in vivo

Emerging Microbes and Infections

卷:11

Yan Liu¹  Hailin Tang²  Zhongtian Qi²  Zhenghan Luo²  Bingan Wu²  Xijing Qian²  Ping Zhao²  Zhenghao Xu²  Jianfeng Xie³  Songying Ouyang⁴  Xiangliang Li⁴  Zhigang Yi⁵  Qibin Leng⁶ 

[1] Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China;

[2] Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, People’s Republic of China;

[3] Fujian Provincial Center for Disease Control and Prevention, Fujian, People’s Republic of China;

[4] Key Laboratory of Innate Immune Biology of Fujian Province, College of Life Sciences, Fujian Normal University, Fujian, People’s Republic of China;

[5] Key Laboratory of Medical Molecular Virology and Department of Medical Microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China;

[6] State Key Laboratory of Respiratory Diseases, Affiliated Cancer Hospital &

关键词: Yellow fever virus;    antiviral agents;    rifamycin antibiotics;    viral entry;    viral replication;   

DOI  :  10.1080/22221751.2022.2049983

来源: DOAJ

【 摘 要 】

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific anti-YFV drugs are available till now. Here, we report that rifapentine is a potent YFV inhibitor in various cell lines by high-throughput drugs screening, acting at both cell entry and replication steps. Kinetic test and binding assay suggest that rifapentine interferes the viral attachment to the target cells. The application of YFV replicon and surface plasmon resonance assay indicates that rifapentine suppresses viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5. Further molecular docking suggests that it might interact with the active centre of RdRp. Rifapentine significantly improves the survival rate, alleviates clinical signs, and reduces virus load and injury in targeted organs both in YFV-infected type I interferon receptor knockout A129−/− and wild-type C57 mice. The antiviral effect in vivo is robust during both prophylactic intervention and therapeutic treatment, and the activity is superior to sofosbuvir, a previously reported YFV inhibitor in mice. Our data show that rifapentine may serve as an effective anti-YFV agent, providing promising prospects in the development of YFV pharmacotherapy.

【 授权许可】

Unknown