Nucleosides for the treatment of respiratory RNA virus infections

Jordan, Paul C; Stevens, Sarah K; Deval, Jerome

The broad-spectrum antiviral effect of ribavirin, a guanosine analog, was first reported in the 1970s. 106, 107 It was found at the time that ribavirin inhibits 16 DNA and RNA viruses, including herpesviruses, vaccinia, VSV, as well as respiratory infections caused by influenza A and B viruses and parainfluenza 1 virus. Ribavirin is currently approved for the treatment of chronic HCV infection in combination therapy and against severe RSV infection in monotherapy. In the case of RSV infection, ribavirin is administered as a small-particle aerosol that requires use of a mask and a tent. Ribavirin was originally developed against influenza based on its efficacy in a mouse model of influenza, 108,109 but its effect in human clinical trials was less clear, so it was not approved for the treatment of influenza. 110 Its clinical use for the treatment of RSV infection via aerosol delivery remains limited due the inconvenient route of administration, lack of clear evidence for efficacy, and safety concerns associated with anemia and risk of teratogenicity.