TY - JOUR
T1 - JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis
AU - Son, Juhee
AU - Huang, Shimeng
AU - Zeng, Qiru
AU - Bricker, Traci L.
AU - Case, James Brett
AU - Zhou, Jinzhu
AU - Zang, Ruochen
AU - Liu, Zhuoming
AU - Chang, Xinjian
AU - Darling, Tamarand L.
AU - Xu, Jian
AU - Harastani, Houda H.
AU - Chen, Lu
AU - Castro, Maria Florencia Gomez
AU - Zhao, Yongxiang
AU - Kohio, Hinissan P.
AU - Hou, Gaopeng
AU - Fan, Baochao
AU - Niu, Beibei
AU - Guo, Rongli
AU - Rothlauf, Paul W.
AU - Bailey, Adam L.
AU - Wang, Xin
AU - Shi, Pei Yong
AU - Martinez, Elisabeth D.
AU - Brody, Steven L.
AU - Whelan, Sean P.J.
AU - Diamond, Michael S.
AU - Boon, Adrianus C.M.
AU - Li, Bin
AU - Ding, Siyuan
N1 - Publisher Copyright:
Copyright © 2022 Son et al.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Antiviral agents
KW - Coronavirus
KW - JIB-04
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85125899189&partnerID=8YFLogxK
U2 - 10.1128/MBIO.03377-21
DO - 10.1128/MBIO.03377-21
M3 - Article
C2 - 35038906
AN - SCOPUS:85125899189
SN - 2161-2129
VL - 13
JO - mBio
JF - mBio
IS - 1
M1 - e03377
ER -