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.