2. Academic Validation
  3. Inhibition of vaccinia virus replication by nitazoxanide

Inhibition of vaccinia virus replication by nitazoxanide

  • Virology. 2018 May;518:398-405. doi: 10.1016/j.virol.2018.03.023.
Sarah E Hickson 1,  Daciana Margineantu 2,  David M Hockenbery 3,  Julian A Simon 2,  Adam P Geballe 4
Affiliations

Affiliations

  • 1 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Microbiology, University of Washington, Seattle, WA 98115, United States.
  • 2 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
  • 3 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Medicine, University of Washington, Seattle, WA 98115, United States.
  • 4 Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Microbiology, University of Washington, Seattle, WA 98115, United States; Department of Medicine, University of Washington, Seattle, WA 98115, United States. Electronic address: ageballe@fhcrc.org.
PMID: 29625403 DOI: 10.1016/j.virol.2018.03.023
Abstract

Nitazoxanide (NTZ) is an FDA-approved anti-protozoal drug that inhibits several bacteria and viruses as well. However, its effect on poxviruses is unknown. Therefore, we investigated the impact of NTZ on vaccinia virus (VACV). We found that NTZ inhibits VACV production with an EC50 of ~2 μM, a potency comparable to that reported for several other viruses. The inhibitory block occurs early during the viral life cycle, prior to viral DNA replication. The mechanism of viral inhibition is likely not due to activation of intracellular innate immune pathways, such as protein kinase R (PKR) or interferon signaling, contrary to what has been suggested to mediate the effects of NTZ against some other viruses. Rather, our finding that addition of exogenous palmitate partially rescues VACV production from the inhibitory effect of NTZ suggests that NTZ impedes adaptations in cellular metabolism that are needed for efficient completion of the VACV replication cycle.

Keywords

Metabolism; Nitazoxanide; Palmitate; Protein kinase R; Vaccinia virus.

Figures
Products