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Various compounds may help advance Zika treatments
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Through a collaborative effort with Johns Hopkins University and Florida State University, researchers at the National Center for Advancing Translational Sciences, part of the NIH, identified two classes of compounds — emricasan and Niclocide — that may be used to inhibit Zika virus replication and reduce its ability to kill brain cells, according to a press release.
This new research will enable the compounds to be studied to help combat Zika virus infection and eliminate the associated current health crisis.
Using NCATS’ drug repurposing screening robots, Wei Zheng, PhD, an NCATS researcher, and colleagues conducted a drug repurposing screening to test three strains of Zika: Asian, African and Puerto Rican, according to the release. They developed an assay using caspase 3, a protein that causes brain cell death when infected by Zika, and then screened 6,000 FDA-approved and investigational compounds. The researchers identified more than 100 promising compounds, including the two compounds effective against Zika.
Emricasan (Conatus Pharmaceuticals) is an investigational drug currently being evaluated in a clinical trial to reduce liver injury and fibrosis and Niclocide (niclosamide, Bayer HealthCare Pharmaceuticals Inc.) is an FDA-approved drug for use in humans to treat worm infections. In addition, researchers identified nine cyclin-dependent kinase (CDK) inhibitors that may also stop Zika virus replication, particularly PHA-690509.
“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small molecule compounds may accelerate the translational process of finding a potential therapy,” Anton Simeonov, PhD, NCATS scientific director, said in the release.
According to the release, the researchers also evaluated the protective effect of these compounds in brain cells after Zika virus infection. They found that emricasan, PHA-690509 and niclosamide effectively reduced neuronal cell death caused by the infection. They also noted that emricasan combined with one of the CKD inhibitors prevented both cell death and virus replication.
“While identifying promising compounds is a first step, our goal at NCATS is to facilitate the translation of these findings for evaluation in the clinic,” Zheng said in the release. “The release of all the compound screening data in this publication and in the public PubChem database opens the door to the research community to do just that.”
The screening efforts of NCATS researchers have enabled the broader research team to quickly translate their earlier discoveries toward work to develop treatments for Zika virus infection, according to the release. Researchers at Johns Hopkins University are working on a mouse model to study the neuroprotective effects of the compounds identified from the screening and studying the mechanism of action of the lead compounds. In addition, Florida State University researchers are testing the efficacy of these compounds in a Zika virus mouse model and also studying the mechanism of action of the lead compounds.
Disclosure: Simeonov and Zheng are employed by the NCATS.