Researchers from University of North Carolina at Chapel Hill Gillings School of Public Health, Vanderbilt University Medical Center (VUMC) and the Emory Institute for Drug Development (EIDD) have discovered in preclinical animal and cell tests that a drug called EIDD-2801 could be a prophylactic or therapeutic for COVID-19 and other coronaviruses. This new drug candidate, originally discovered at Emory, has similarities to Gilead’s remdesivir but also may possess some distinct advantages in that it can be taken orally and may address severe lung symptoms. The team expects to move to clinical trials later this spring to add to the competitive race for approved COVID-19 treatments.
A multicenter team of NIH-funded investigators are in hot pursuit of an exciting potential drug that shows potential to target COVID-19 and other coronaviruses. Their findings were recently published online in Science Translational Medicine. TrialSite News breaks down these findings for the TrialSite Network. The experimental drug, known as EIDD-2801, was developed in the laboratories of the Emory Institute for Drug Development (EIDD).
What is EIDD-2801?
EIDD-2801 is a new drug that acts to interfere with the coronavirus’ replication process. In this way the preclinical (laboratory)-based drug is comparable to Gilead’s’ remdesivir which of course is currently being tested in clinical trials targeting COVID-19 patients. However, the researchers report that EIDD-2801 actually can be take as a pill, which is a great benefit given Remdesivir must be taken intravenously. Moreover, the research team reports that EIDD-2801, when used as a prophylactic, can actually prevent severe lung damage in infected mice when the treatment was administered between 12 and 48 hours after the infection commenced.
It turns out EIDD-2801 is actually an orally available form of the antiviral compound EIDD-1931. In 2019, Emory University preclinical researchers published the results of a study identifying EIDD-1931 as a drug target for New World alphaviruses, such as Venezuelan, Eastern and Western equine encephalitis viruses, which can lead to deadly consequences from meningoencephalitis. They noted that they “identified and pursued preclinical characterization of ribonucleoside analog EID-1931 (β-D-N4-hydroxycytidine, NHC), which has shown broad activity against alphaviruses in vitro and has a very high genetic barrier for development of resistance.”
The dug was also evaluated and analyzed in a 2019 study by one of the senior researchers, such as Mark R Denison at VUMC, that first reported that EIDD-1931 blocked the replication of a broad spectrum of coronaviruses.
So, to summarize, EIDD-2801 is actually an orally available form of EIDD-1931, which shows strong antiviral activity against a number of viruses including coronaviruses. The university researchers have, among other things, been trying to identify the mechanism of action of the antiviral nucleoside in coronaviruses.
Who are the key players in this Collaboration?
Researchers at the UNC-Chapel Hill Gillings School of Public Health are playing a key role in the development and testing of EIDD-2801. Also, virologists from the lab of William R. Kenan Jr. Distinguished Professor of epidemiology Ralph Baric collaborate with colleagues in the lab of Mark Denison, Edward Claiborne Stahlman Professor of pediatrics at Vanderbilt University Medical Center (VUMC), along with George Painter, chief executive officer of the nonprofit DRIVE (Drug Innovation Ventures at Emory) and director of the Emory Institute of Drug Development (EIDD)—the place where EIDD-2801 was discovered.
When are Clinical Trials Anticipated?
The authors report that actual studies in humans are expected later this spring. The hope is that of course if these studies are successful the drug could not only be used to limit the spread of SARS-CoV-2 but also control future outbreaks of other emerging coronaviruses.
Do the Researchers Include Data in their Published Results?
Yes. The team’s work—published online April 6 by the journal Science Translational Medicine, includes data from cultured human lung cells infected with SARS-CoV-2 as well as mice infected with related coronaviruses SARS-CoV and MERS-CoV.
National Institutes of Health (NIH) is a backbone for research in the United States. Through its various institutes, it funds billions of dollars of important research. In fact in relation to this early-stage, preclinical research study, the lead antiviral scientist at the Denison Lab at VUMC noted, “This work shows the importance of ongoing National Institutes of Health (NIH) support for collaborative research to develop antivirals for all pandemic viruses, not just coronaviruses.”
- Antiviral Drug Discovery and Development Center (5U19AI109680 and (1U19AI142759) awarded a grant to Mark Denison and Ralph S. Baric
- A Partnership grant from the National Institutes of Allergy and Infectious Disease (NIAID, 5R01AI132178) awarded to Timothy P Sheahan and Ralph S. Baric
- NIAID R01 grant (Al108197) to Mark Denison and Ralph S. Baric
- NIAID contract ( HHSN272201500008C ) was awarded to George Painter and the Emory Institute for Drug Development—with a subcontract to Ralph S. Baric and Mark Denison
- NIH supported funds to procure tissue from the Marsico lung institute
- Cystic Fibrosis Foundation grant
UNC is pursuing IP protection for Primer ID which is a highly sensitive high-fidelity deep sequencing approach, which uses barcoded degenerate primers and Illumina indexed libraries to determine accurate mutation rates on viral RNA production. According to the authors in their disclosure, Ralph Swanstrom (UNC) did receive nominal royalties but didn’t disclose for what. It was disclosed that various patents from the Emory researchers were utilized (again Emory discovered the underlying drug).
Timothy P. Sheahan, PhD, University of North Carolina, Gillings School of Global Public Health
George Painter, President and CEO, The Emory Institute for Drug Development
Andrea J. Pruijssers, PhD, Research Assistant, Professor Infectious Disease
Maria Agostini, Postdoctoral Fellow, Pathology, Microbiology, Immunology, Denison Lab, Vanderbilt University
Ronald Swanstrom, PhD, Charles P. Postelle Jr. Distinguished Professors of Biochemistry, Director, UNC Center for AIDS Research; Microbiology and Immunology
Mark R. Denison, MD, Professor of Pediatrics, Professor of Pathology, Microbiology and Immunology, Craig-Weaver Chair in Pediatrics, Vanderbilt University Medical Center (VUMC)
Ralph S. Baric, PhD, William R. Kenan, Jr. Distinguished Professor, Department of Epidemiology; Professor Department of Microbiology and Immunology, Member Lineberger Comprehensive Cancer Center, University of North Carolina, Gillings School of Global Public Health
Note that there were 28 authors and to see other authors follow the link to the source at Science Translational Medicine.
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