JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis
Juhee Son,
Shimeng Huang,
Qiru Zeng,
Traci L. Bricker,
James Brett Case,
Jinzhu Zhou,
Ruochen Zang,
Zhuoming Liu,
Xinjian Chang,
Tamarand L. Darling,
Jian Xu,
Houda H. Harastani,
Lu Chen,
Maria Florencia Gomez Castro,
Yongxiang Zhao,
Hinissan P. Kohio,
Gaopeng Hou,
Baochao Fan,
Beibei Niu,
Rongli Guo,
Paul W. Rothlauf,
Adam L. Bailey,
Xin Wang,
Pei-Yong Shi,
Elisabeth D. Martinez,
Steven L. Brody,
Sean P. J. Whelan,
Michael S. Diamond,
Adrianus C. M. Boon,
Bin Li,
Siyuan Ding
Affiliations
Juhee Son
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Shimeng Huang
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Qiru Zeng
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Traci L. Bricker
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
James Brett Case
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
Jinzhu Zhou
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Ruochen Zang
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Zhuoming Liu
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Xinjian Chang
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Tamarand L. Darling
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
Jian Xu
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
Houda H. Harastani
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
Lu Chen
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA
Maria Florencia Gomez Castro
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Yongxiang Zhao
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Hinissan P. Kohio
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Gaopeng Hou
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Baochao Fan
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Beibei Niu
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Rongli Guo
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Paul W. Rothlauf
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Adam L. Bailey
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
Xin Wang
Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, China
Pei-Yong Shi
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
Elisabeth D. Martinez
Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas, USA
Steven L. Brody
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
Sean P. J. Whelan
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Michael S. Diamond
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Adrianus C. M. Boon
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Bin Li
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation, Base of Ministry of Science and Technology, Nanjing, China
Siyuan Ding
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
ABSTRACT Pathogenic coronaviruses are a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified small-molecule inhibitors that potently block the replication of severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with a 50% effective concentration of 695 nM, with a specificity index of greater than 1,000. JIB-04 showed in vitro antiviral activity in multiple cell types, including primary human bronchial epithelial cells, 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. IMPORTANCE The coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is an ongoing public health disaster worldwide. Although several vaccines are available as a preventive measure and the FDA approval of an orally bioavailable drug is on the horizon, there remains a need for developing antivirals against SARS-CoV-2 that could work on the early course of infection. By using infectious reporter viruses, we screened small-molecule inhibitors for antiviral activity against SARS-CoV-2. Among the top hits was JIB-04, a compound previously studied for its anticancer activity. Here, we showed that JIB-04 inhibits the replication of SARS-CoV-2 as well as different DNA and RNA viruses. Furthermore, JIB-04 conferred protection in a porcine model of coronavirus infection, although to a lesser extent when given as therapeutic rather than prophylactic doses. Our findings indicate a limited but still promising utility of JIB-04 as an antiviral agent in the combat against COVID-19 and potentially other viral diseases.
