The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus

Jasenosky, Luke D.; Cadena, Cristhian; Mire, Chad E.; Borisevich, Viktoriya; Haridas, Viraga; Ranjbar, Shahin; Nambu, Aya; Bavari, Sina; Soloveva, Veronica; Sadukhan, Supriya; Cassell, Gail H.; Geisbert, Thomas W.; Hur, Sun; Goldfeld, Anne E.

Here, we have shown that the FDA-approved small molecule drug NTZ broadly amplifies cytoplasmic RNA sensing and type I IFN pathways and strongly inhibits replication of EBOV and VSV. Our data indicate that NTZ's amplification of RIG-I and PKR activities overcomes EBOV VP35's ability to prevent the triggering of these critical host antiviral factors. By contrast, in the case of VSV, NTZ-mediated amplification of RIG-I signaling and induction of GADD34 expression, both contribute to the drug's anti-VSV activity. Thus, the wide array of innate immune activities that NTZ amplifies provides cells with the capacity to resist productive infection by diverse viruses like EBOV and VSV that engage distinct host evasion mechanisms.