The leprosy drug clofazimine kills coronaviruses, including SARS-CoV-2, in cells and prevents the deadly, out-of-control immune response in hamsters infected with COVID-19, researchers report. The results suggest that the drug, which can be taken in pill form, could be used to treat COVID-19 outside hospital settings and that it could be a therapy for future coronavirus outbreaks. Kwok-Yung Yuen and Ren Sun of the University of Hong Kong and Sumit K. Chanda of the Sanford Burnham Prebys Medical Discovery Institute led the research effort (Nature 2021, DOI: 10.1038/s41586-021-03431-4). The team identified clofazimine, which was approved by the US Food and Drug Administration as a leprosy treatment in 1986, by screening the ReFRAME collection, a library of about 12,000 drugs and drug candidates. Further studies showed that clofazimine prevents SARS-CoV-2 infection by preventing the virus’s spike protein from fusing with cells, a key step in infection, and by disrupting the RNA-copying process the virus uses to replicate. Hamsters given clofazimine before being infected with SARS-CoV-2, as well as hamsters given it after being infected, had lower amounts of the virus in their lungs than those that did not get the drug at all. Clofazimine also worked synergistically with the antiviral compound remdesivir in hamster studies. Clofazimine is currently in Phase 2 trials in combination with interferon β-1b for people hospitalized with COVID-19. The researchers are trying to secure funding to study the drug as a stand-alone COVID-19 treatment.