Nifuroxazide Prevents Chikungunya Virus Infection Both <i>In Vitro</i> and <i>In Vivo</i> via Suppressing Viral Replication
Yangang Liu,
Mingxiao Xu,
Binghui Xia,
Zhuoyue Qiao,
Yanhua He,
Yan Liu,
Zhendong Pan,
Congcong Zhang,
Haoran Peng,
Xuesong Liang,
Ping Zhao,
Hailin Tang,
Xu Zheng
Affiliations
Yangang Liu
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Mingxiao Xu
Department of Infection Diseases, First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
Binghui Xia
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Zhuoyue Qiao
Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, China
Yanhua He
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Yan Liu
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Zhendong Pan
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Congcong Zhang
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Haoran Peng
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Xuesong Liang
Department of Infection Diseases, First Affiliated Hospital of Navy Military Medical University, Shanghai 200433, China
Ping Zhao
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Hailin Tang
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Xu Zheng
Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China
Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.
