Researchers at NCATS Identify Compounds to Fight Zika Virus

Researchers at the NIH’s National Center for Advancing Translational Sciences (NCATS), working with colleagues at Johns Hopkins and Florida State University have identified compounds that “potentially can be used to inhibit Zika virus replication and reduce its ability to kill brain cells.”

As Zika continues to confound public health officials and clinicians across the Western Hemisphere—and beyond—collaborative efforts ongoing at the US National Institutes of Health (NIH) may be making inroads into the development of an effective vaccine against the virus.

Researchers at the NIH’s National Center for Advancing Translational Sciences (NCATS), working with colleagues at Johns Hopkins and Florida State University have identified compounds that “potentially can be used to inhibit Zika virus replication and reduce its ability to kill brain cells,” according to a statement released by the agency. The hope is that these compounds can be assessed for their prophylactic potential within the research community. Their findings were published on August 29 in the journal Nature Medicine, and build on earlier studies at both universities that determined that Zika virus infects brain cells early in development.

“The Zika virus poses a global health threat,” Anton Simeonov, PhD, scientific director at NCATS said in the press release. “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.”

Researchers across the globe have been assessing various approaches to virus prevention, from mosquito control to possible vaccines. However, while progress has been significant, given the relatively short amount of time that has elapsed since Zika resurfaced in Brazil in late 2014, the biggest accomplishment to date has arguably been the identification of animal models for use in research.

However, that may soon change. Researchers at NCATS have been actively using the agency’s “drug repurposing screening robots” in Zika-related studies, and they have identified two compounds that appear to be effective against the virus: the antiviral emricasan (IDN-6556, Conatus Pharmaceuticals) and the old-line teniacide niclosamide. Emricasan is an investigational drug currently in clinical trials for use as a treatment for liver injury and fibrosis. Niclosamide, meanwhile, has been approved by the US Food and Drug Administration (FDA) for use in humans to treat worm infections.

NCATS researcher Wei Zheng, PhD, and his team tested three strains of Zika (Asian, African, and Puerto Rican) and developed an assay using caspase 3, a protein that causes brain cell death when infected by the virus. They then screened more than 6,000 FDA-approved and investigational compounds and identified more than 100 “promising compounds,” which were then evaluated for their potential protective effects in brain cells after Zika virus infection. Emiracsan and niclosamide as well as the CDK inhibitor PHA-690509 (Symanis) were found to be effective at reducing the neuronal cell death caused by Zika, with emricasan capable of preventing cell death and niclosamide and the CDK inhibitor effective in preventing virus replication. In addition, the researchers found that the CDK inhibitors may be useful in treating non-pregnant patients at increased risk for Guillain-Barré syndrome and other conditions associated with Zika infection.

“Using the NCATS drug repurposing platform for emerging infectious diseases can help rapidly identify potential treatments for urgent needs such as the Zika virus,” Dr. Zheng said in the NCATS statement. “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. 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.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.