文献类型： 外文期刊

作者： Son, Juhee ¹ ; Huang, Shimeng ³ ; Zeng, Qiru ¹ ; Bricker, Traci L. ⁴ ; Case, James Brett ⁴ ; Zhou, Jinzhu ³ ; Zang, Ruochen ¹ ; Liu, Zhuoming ¹ ; Chang, Xinjian ³ ; Darling, Tamarand L. ⁴ ; Xu, Jian ⁶ ; Harastani, Houda H. ⁴ ; Chen, Lu ⁷ ; Castro, Maria Florencia Gomez ¹ ; Zhao, Yongxiang ³ ; Kohio, Hinissan P. ¹ ; Hou, Gaopeng ¹ ; Fan, Baochao ³ ; Niu, Beibei ³ ; Guo, Rongli ³ ; Rothlauf, Paul W. ¹ ; Bailey, Adam L. ⁹ ; Wang, Xin ⁵ ; Shi, Pei-Yong ¹⁰ ; Martinez, Elisabeth D. ¹¹ ; Brody, Steven L. ⁶ ; Whelan, Sean P. J. ¹ ; Diamond, Michael S. ¹ ; Boon, Adrianus C. M. ¹ ; Li, Bin ³ ; Ding, Siyuan ¹ ;

作者机构： 1.Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

2.Washington Univ, Program Mol Cell Biol, St Louis, MO 63110 USA

3.Jiangsu Acad Agr Sci, Inst Vet Med, Jiangsu Key Lab Food Qual & Safety, Base Minist Sci & Technol,State Key Lab Cultivat, Nanjing, Peoples R China

4.Washington Univ, Sch Med, Dept Med, Div Infect Dis, St Louis, MO 63110 USA

5.Ocean Univ China, Key Lab Marine Drugs, Minist Educ, Qingdao, Peoples R China

6.Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA

7.NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA

8.Harvard Med Sch, Program Virol, Boston, MA 02115 USA

9.Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

10.Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA

11.UT Southwestern Med Ctr, Dept Pharmacol, Dallas, TX USA

关键词： JIB-04; SARS-CoV-2; antiviral agents; coronavirus

期刊名称：MBIO （ 影响因子：7.786； 五年影响因子：8.483 ）

ISSN： 2150-7511

年卷期： 2022 年 13 卷 1 期

页码：

收录情况： SCI

摘要： 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.