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Nafamostat mesylate as a broad-spectrum candidate for the treatment of flavivirus infections by targeting envelope proteins.
Yan, Yunzheng; Yang, Jingjing; Xiao, Dian; Yin, Jiye; Song, Mengwen; Xu, Yijie; Zhao, Lei; Dai, Qingsong; Li, Yuexiang; Wang, Cui; Wang, Zhuang; Ren, Xiaofeng; Yang, Xiaotong; Ni, Jie; Liu, Miaomiao; Guo, Xiaojia; Li, Wei; Chen, Xingjuan; Liu, Zhiqiang; Cao, Ruiyuan; Zhong, Wu.
Afiliação
  • Yan Y; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Yang J; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
  • Xiao D; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Yin J; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Song M; Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
  • Xu Y; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Zhao L; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Dai Q; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Li Y; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Wang C; Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
  • Wang Z; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, China.
  • Ren X; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Yang X; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Ni J; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Liu M; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Guo X; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Li W; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • Chen X; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, China.
  • Liu Z; Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
  • Cao R; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. Electronic address: 21cc@163.com.
  • Zhong W; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. Electronic address: zhongwu@bmi.ac.cn.
Antiviral Res ; 202: 105325, 2022 06.
Article em En | MEDLINE | ID: mdl-35460703
Epidemics caused by flaviviruses occur globally; however, no antiviral drugs treating flaviviruses infections have yet been developed. Nafamostat (NM) is a protease inhibitor approved for pancreatitis and anti-coagulation. The anti-flavivirus potential of NM has yet to be determined. Here, utilizing in vitro and in vivo infection assays, we present that NM effectively inhibits Zika virus (ZIKV) and other flaviviruses in vitro. NM inhibited the production of ZIKV viral RNA and proteins originating from Asia and African lineage in human-, mouse- and monkey-derived cell lines and the in vivo anti-ZIKV efficacy of NM was verified. Mode-of-action analysis using time-of-drug-addition assay, infectivity inhibition assay, surface plasmon resonance assay, and molecular docking revealed that NM interacted with viral particles and blocked the early stage of infection by targeting the domain III of ZIKV envelope protein. Analysing the anti-flavivirus effects of NM-related compounds suggested that the antiviral effect depended on the unique structure of NM. These findings suggest the potential use of NM as an anti-flavivirus candidate, and a novel drug design approach targeting the flavivirus envelope protein.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Benzamidinas / Flavivirus / Zika virus / Guanidinas Limite: Animals / Humans Idioma: En Revista: Antiviral Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Benzamidinas / Flavivirus / Zika virus / Guanidinas Limite: Animals / Humans Idioma: En Revista: Antiviral Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Holanda