April 6, 2020

VUMC team aids development of potential antiviral drug for COVID-19

Researchers at Vanderbilt University Medical Center are playing a key role in the development of a potential new antiviral drug to treat COVID-19.


by Bill Snyder

Researchers at Vanderbilt University Medical Center are playing a key role in the development of a potential new antiviral drug to treat COVID-19.

The drug, named EIDD-1931, was developed at the Emory Institute for Drug Development in Atlanta. In November, Mark Denison, MD, and colleagues at VUMC reported that EIDD-1931 blocked replication of a broad spectrum of coronaviruses in laboratory tests and prevented these viruses from developing resistance against it.

The drug study team includes (back row from left) Jim Chappell, MD, PhD, Andrea Pruijssers, PhD, Mark Denison, MD, (front row from left) postdoctoral fellow Maria Agostini, PhD, graduate student Jennifer Gribble Bowser, and senior research specialists Laura Stevens, MS, Tia Hughes, MS, and Xioatao Lu, MS. Current lab members also include research fellow Jordan Anderson-Daniels, PhD, and research assistant Amelia George, MS. (photo was taken last year)

Andrea Pruijssers, PhD, research assistant professor of Pediatrics and the lead antiviral scientist in Denison’s lab, provided the first evidence of the drug’s potent activity against SARS-CoV-2, the virus that causes COVID-19.

The VUMC researchers also contributed to a subsequent animal study conducted at the University of North Carolina at Chapel Hill.

That paper, 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 the related coronaviruses SARS-CoV and MERS-CoV.

The study found that EIDD-2801, a form of EIDD-1931 that can be taken orally, prevented severe lung injury in infected mice. When given 12 or 24 hours after infection had begun, the drug reduced the degree of lung damage and weight loss in mice.

If clinical studies in humans, expected to begin later this spring, are successful, EIDD-2801 could not only help stop the spread of SARS-CoV-2, but it also could control future outbreaks of other emerging coronaviruses, said Denison, an internationally known authority on coronavirus biology.

“We are amazed at the ability of EIDD-1931 and -2801 to inhibit all tested coronaviruses and the potential for oral treatment of COVID-19,” Pruijssers said. “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.”

The inter-institutional collaborators, supported by an NIH grant through the University of Alabama at Birmingham, also performed the preclinical development of remdesivir, another antiviral drug currently in clinical trials of patients with COVID-19.

In the paper published today, Maria Agostini, PhD, a postdoctoral fellow in Denison’s lab, demonstrated that viruses showing resistance to remdesivir are more highly inhibited by EIDD-1931.

Since 2014 Denison and his colleagues have investigated the antiviral drug remdesivir, a potential COVID-19 treatment now in clinical trials in the United States and China. Pruijssers has also demonstrated that remdesivir is effective against SARS-CoV-2.

Currently no antiviral drugs have been approved to treat SARS-CoV-2 or any of the other coronaviruses that cause human disease. Since early January when the outbreak was first reported in China, SARS-CoV-2 has infected more than 1.3 million people worldwide and caused nearly 74,000 deaths.

Denison’s lab also will be involved in a phase 1 clinical trial that is testing antibody responses to a potential vaccine against SARS-CoV-2 designed and produced by Massachusetts-based biotechnology firm Moderna Inc.

Denison, the Craig-Weaver Professor of Pediatrics, directs the Division of Pediatric Infectious Diseases in the Department of Pediatrics.

The VUMC research is supported by National Institutes of Health grants AI109680, AI142759, AI112541, AI133952 and GM065086.