Amid the worsening Ebola outbreak in the Congo, now threatening to spill into Rwanda, a new study suggests that an existing, FDA-approved drug called nitazoxanide could potentially help contain this deadly, highly contagious infection. In meticulous experiments in human cells, described today in iScience, the drug significantly amplified immune responses to the virus and inhibited Ebola replication.
Led by Anne Goldfeld, MD, of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, the study also showed how the drug works: It enhances the immune system’s ability to detect Ebola, normally impeded by the virus.
Nitazoxanide, or NTZ, is currently used to treat gastrointestinal infections caused by such parasites as Giardia and Cryptosporidium. It’s been shown to be safe and even comes in a formulation for children. Goldfeld hopes that, with further testing and validation, it could be part of the solution for Ebola.
“Currently, there is no easily deployable therapy for Ebola virus,” she says. “There are some very promising vaccines, but there is no oral, inexpensive medication available.”
The Ebola virus caused more than 10,000 deaths in the 2014–2016 West African epidemic and more than 1,800 lives (as of August 6) in the current outbreak in the Democratic Republic of the Congo. The virus is very good at evading human immune defenses. Though small, it has two genes specifically devoted to blocking immune responses.
Goldfeld and collaborators Chad Mire, PhD and Thomas Geisbert, PhD at the University of Texas Medical Branch, Galveston, showed in Biosafety Level 4 laboratory experiments that NTZ inhibits the Ebola virus (isolated from an earlier outbreak). Additional experiments performed in collaboration with Sun Hur, PhD of Boston Children’s showed that NTZ works by broadly amplifying the interferon pathway and cellular viral sensors, including two known as RIG-I and PKR.
What we’ve been able to do is enhance the Ebola detection response.
By deleting RIG-I and PKR in human cells through CRISPR editing, Goldfeld and her University of Texas colleagues showed that NTZ works through these molecules to inhibit Ebola virus.
“Ebola masks RIG-I and PKR, so that cells don’t perceive that the virus is inside,” Goldfeld explains. “This lets Ebola get a foothold in the cell and race ahead of the immune response. What we’ve been able to do is enhance the host viral detection response with NTZ. It’s a new path in treating Ebola.”
Goldfeld hopes to move into animal studies soon, especially given that NTZ has already been used in millions of people with minimal side effects. If effective, it could then be easily repurposed for Ebola treatment or prevention, she believes.
Luke Jasenosky, PhD, of Boston Children’s Hospital (now at Profectus Biosciences) was the study’s first author. The study was funded by the Annenberg Foundation, John Moores, the National Institutes of Health, and the Ragon Institute. The paper can be accessed at https://doi.org/10.1016/j.isci.2019.07.003.
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