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.

To test whether NTZ enhances sensing by the RLR pathway, we overexpressed full-length RIG-I or melanoma differentiation-associated protein 5 (MDA5), the two major RLR proteins, in human embryonic kidney (HEK) 293T cells that were co-transfected with an IFN-b promoter-driven luciferase reporter plasmid (IFN-b LUC). We then examined whether NTZ augmented IFN-b promoter activity in the presence or absence of a viral nucleic acid analog, the synthetic dsRNA poly I:C. NTZ pretreatment enhanced poly I:C-stimulated IFN-b promoter activity in RIG-I-( Figure 1A , left) and in MDA5-( Figure 1A , right) overexpressing cells in a dose-dependent manner ( Figure 1A ). In the case of MDA5 overexpression, NTZ's effect on IFN-b reporter gene activity was evident even in the absence of poly I:C treatment ( Figure 1A , right).