BOSTON (August 8, 2019) - 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, led by Boston Children's Hospital, the drug significantly amplified immune responses to Ebola and inhibited Ebola replication.
The study, published in the Cell Press journal iScience, 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 parasites such as Giardia and Cryptosporidium. It has been shown to be safe and even comes in a formulation for children. Study leader Anne Goldfeld, MD, of the Program in Cellular and Molecular Medicine at Boston Children's, 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."
Outsmarting Ebola
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 6th) in the current outbreak in the Democratic Republic of the Congo. The virus is very good at evading human immune defenses. Though very small, it has two genes 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. By deleting RIG-I and PKR in human cells through CRISPR editing, Goldfeld and 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 Ebola is inside," explains Goldfeld. "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 thus be easily repurposed for Ebola treatment or prevention.
###
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 (AI125075, AI106912, AI111784, U19AI109711), and the Ragon Institute. The paper can be accessed at https://doi.org/10.1016/j.isci.2019.07.003.
About Boston Children's Hospital
Boston Children's Hospital is ranked the #1 children's hospital in the nation by U.S. News & World Report and is the primary pediatric teaching affiliate of Harvard Medical School. Home to the world's largest research enterprise based at a pediatric medical center, its discoveries have benefited both children and adults since 1869. Today, 3,000 researchers and scientific staff, including 8 members of the National Academy of Sciences, 18 members of the National Academy of Medicine and 12 Howard Hughes Medical Investigators comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's is now a 415-bed comprehensive center for pediatric and adolescent health care. For more, visit our Discoveries blog and follow us on social media @BostonChildrens, @BCH_Innovation, Facebook and YouTube.
Journal
iScience