Treatment options for CoVs are largely lacking. In this article the authors show that clofazimine, an anti-leprosy drug with a favourable safety profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 and MERS-CoV replication in multiple in vitro systems. The FDA-approved molecule was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and faecal viral shedding, and also mitigated inflammation associated with viral infection. Combinatorial application of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted upper respiratory tract viral shedding. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. The authors concluded that their data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2 , and, possibly most importantly, emerging CoVs of the future. Yuan, S., et al. Clofazimine broadly inhibits coronaviruses including SARS-CoV-2 . Nature (2021).