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Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model
Juhee Son; Shimeng Huang; Qiru Zeng; Traci L. Bricker; James Brett Case; Jinzhu Zhou; Ruochen Zang; Zhuoming Liu; Xinjian Chang; Houda H. Harastani; Lu Chen; Maria Florencia Gomez Castro; Yongxiang Zhao; Hinissan Pascaline Kohio; Gaopeng Hou; Baochao Fan; Beibei Niu; Rongli Guo; Paul W. Rothlauf; Adam L. Bailey; Xin Wang; Pei-Yong Shi; Elisabeth D. Martinez; Sean P. J. Whelan; Michael S. Diamond; Adrianus C.M. Boon; Bin Li; Siyuan Ding.
Afiliação
  • Juhee Son; Washington University School of Medicine
  • Shimeng Huang; Jiangsu Academy of Agricultural Sciences
  • Qiru Zeng; Washington University School of Medicine
  • Traci L. Bricker; Washington University School of Medicine
  • James Brett Case; Washington University School of Medicine
  • Jinzhu Zhou; Jiangsu Academy of Agricultural Sciences
  • Ruochen Zang; Washington University School of Medicine
  • Zhuoming Liu; Washington University School of Medicine
  • Xinjian Chang; Jiangsu Academy of Agricultural Sciences
  • Houda H. Harastani; Washington University School of Medicine
  • Lu Chen; National Institutes of Health
  • Maria Florencia Gomez Castro; Washington University School of Medicine
  • Yongxiang Zhao; Jiangsu Academy of Agricultural Sciences
  • Hinissan Pascaline Kohio; Washington University School of Medicine
  • Gaopeng Hou; Washington University School of Medicine
  • Baochao Fan; Jiangsu Academy of Agricultural Sciences
  • Beibei Niu; Jiangsu Academy of Agricultural Sciences
  • Rongli Guo; Jiangsu Academy of Agricultural Sciences
  • Paul W. Rothlauf; Washington University School of Medicine
  • Adam L. Bailey; Washington University School of Medicine
  • Xin Wang; Ocean University of China
  • Pei-Yong Shi; University of Texas Medical Branch
  • Elisabeth D. Martinez; UT Southwestern Medical Center
  • Sean P. J. Whelan; Washington University School of Medicine
  • Michael S. Diamond; Washington University School of Medicine
  • Adrianus C.M. Boon; Washington University School of Medicine
  • Bin Li; Jiangsu Academy of Agricultural Sciences
  • Siyuan Ding; Washington University School of Medicine
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-312165
ABSTRACT
Pathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 695 nM, with a specificity index of greater than 1,000. JIB-04 showed in vitro antiviral activity in multiple cell types against several DNA and RNA viruses, including porcine coronavirus transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved weight gain and survival. These results highlight the potential utility of JIB-04 as an antiviral agent against SARS-CoV-2 and other viral pathogens.
Licença
cc_by_nc_nd
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Preprint