Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model.

•In cell culture models, low-micromolar doses of alisporivir block SARS-CoV and MERS-CoV replication.•Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture.•Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mouse model.•Cyclophilin-binding drugs should be explored further in the context of host-directed anti-coronaviral strategies.