alisporivir and Severe-Acute-Respiratory-Syndrome

Currently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication.

Topics: Animals; Antiviral Agents; Cell Line; Cells, Cultured; Coronavirus Infections; Cyclosporine; Cytopathogenic Effect, Viral; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Mice; Middle East Respiratory Syndrome Coronavirus; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Virus Replication