Nitazoxanide (NTZ), approved by the US Food and Drug Administration (FDA) in 2004 for the treatment of diarrhea caused by parasitic worms or protozoa, has shown activity against Ebola virus in a new study by investigators at Boston Children’s Hospital.
The development of therapeutics to treat Ebola is often overshadowed by the much more public race to develop an effective vaccine but, in the new study published in the Cell Press journal iScience
, the research team deciphered that the drug boosts the ability of specific viral sensors to detect the virus when infected, which then sparks an antiviral immune response.
“We found that NTZ amplified the cell’s RNA sensing and interferon pathways and significantly inhibited Ebola virus replication,” Anne Goldfeld, MD, of the Program in Cellular and Molecular Medicine at Boston Children's and senior author on the study, told Contagion®
Goldfeld and colleagues found that NTZ significantly increased activities of 2 viral sensing molecules known to be masked by Ebola virus when it enters a cell—retinoic-acid-inducible protein I (RIG-I) and protein kinase R (PKR). The research team showed that by increasing the activities of RIG-I and PKR, NTZ inhibited Ebola virus replication in human cells, counteracting the virus’ ability to evade detection. “NTZ shifts the balance so that the cell can overcome Ebola’s ability to escape detection and results in triggering the natural host response of a cell to being infected,” said Goldfeld.
Interestingly, NTZ also inhibited another virus responsible for vesicular stomatitis virus disease in animals through amplifying a different virus responsive gene along with RIG-I.
“These studies indicate that NTZ could potentially be useful in viruses that have different immune evasion strategies because it broadly activates the antiviral response that is triggered once a pathogen comes into the cell,” Goldfeld told Contagion®
“NTZ is an inexpensive drug that is well-tolerated with few side effects in humans, and even has a liquid preparation that can be used in young children,” she concluded. “One could imagine that, if it proves effective in inhibiting Ebola in animal studies, this drug could be very useful for the treatment of Ebola in the growing current outbreaks in the Democratic Republic of the Congo.”
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