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.

Synthetic RLR agonists for the treatment of viruses have generated much interest (Yong and Luo, 2018) . However, because RLRs are expressed in most human tissues and the inflammatory response to their induction is highly variable person to person, there is concern that therapeutic approaches employing RNA agonists will be associated with unacceptable inflammatory side effects (Elion and Cook, 2018). Intriguingly, NTZ has been used extensively with an excellent safety profile in adults and children for treatment of parasitic infections (Doumbo et al., 1997; Hussar, 2004; Rossignol et al., 1998) , and for viral diseases such as HCV (Rossignol et al., 2008 (Rossignol et al., , 2009a and influenza (Haffizulla et al., 2014) . Notably, our findings indicate that NTZ modulate the innate immune response after a pathogen has entered a susceptible target cell, when amplification of natural immune control of viral infection is needed. In the case of viruses like EBOV that employ immune evasion mechanisms to avoid triggering the innate immune response, such a therapeutic profile is attractive. Although identification of NTZ's upstream target is outside the scope of this article, we anticipate that these studies, which are underway, will be of great value in unraveling host pathways that lead to cell-intrinsic control of Ebola.