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.

We next analyzed EBOV replication in the CRISPR/dCas9-RIG-I-KD, PKR-KD, and GADD34-KD A549 cells under biosafety level 4 conditions to determine the individual roles of these antiviral proteins in restricting EBOV growth. Both RIG-I and PKR depletion led to significantly increased EBOV Kikwit replication (Figure 4A) , with an increase of greater than a log unit by 72 h post-infection when compared with control cells ( Figure 4A , right). This experiment demonstrates the importance of both factors in host control of EBOV infection. By contrast, although GADD34 depletion resulted in higher EBOV titers at 48 h, it did not impact EBOV growth by 72 h post-infection ( Figure 4A, right) . Thus, unlike what we found with VSV, GADD34 plays a limited role in restricting EBOV growth in A549 cells.