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

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms. Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV.

Original languageEnglish (US)
Pages (from-to)1279-1290
Number of pages12
JournaliScience
Volume19
DOIs
StatePublished - Sep 27 2019

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Keywords

  • Immune Response
  • Mechanism of Action
  • Pathogenic Organism
  • Viral Microbiology

ASJC Scopus subject areas

  • General

Cite this

Jasenosky, L. D., Cadena, C., Mire, C. E., Borisevich, V., Haridas, V., Ranjbar, S., Nambu, A., Bavari, S., Soloveva, V., Sadukhan, S., Cassell, G. H., Geisbert, T. W., Hur, S., & Goldfeld, A. E. (2019). The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus. iScience, 19, 1279-1290. https://doi.org/10.1016/j.isci.2019.07.003