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.

Our data also show that the activities of factors downstream of the RLRs are amplified by NTZ. Both overexpressed MAVS and constitutively phosphorylated IRF3 activities were amplified in response to NTZ stimulation, resulting in increased type I IFN promoter activity. NTZ also enhanced type I IFN-induced mRNA synthesis of ISGs Mx1, IFI27, and IFITM3. IFITM3 is a critical restriction factor for both EBOV (Huang et al., 2011) and VSV (Huang et al., 2011; Weidner et al., 2010) , and Mx1 has been shown to inhibit VSV infection (Staeheli and Pavlovic, 1991) . Thus, NTZ's ability to amplify both proximal and distal aspects of the viral RNA sensing and type I IFN pathways allows for a broad and effective antiviral response to develop in cells that are immediate viral targets and in neighboring cells yet to be infected.