Scientists in Ralph Baric’s lab at UNC are playing a key role in the development and testing of a new drug, called EIDD-2801, that could change the way doctors treat COVID-19. The drug shows promise in reducing lung damage, has finished testing in mice and will soon move to human clinical trials.
As of Monday, the novel coronavirus SARS-CoV-2 has infected more than 1 million people with COVID-19 and caused more than 70,000 deaths in a worldwide pandemic. Currently, no antiviral drugs have been approved to treat SARS-CoV-2 or any of the other coronaviruses that cause human disease.
Virologists in Baric’s lab in the Gillings School of Global Public Health are working with colleagues in the Vanderbilt University Medical Center lab of Baric’s longtime collaborator, Mark Denison; and with George Painter, chief executive officer of the nonprofit Drug Innovation Ventures at Emory and director of the Emory Institute for Drug Development where EIDD-2801 was discovered. Baric is UNC’s Kenan Distinguished Professor of epidemiology.
Clinical studies of EIDD-2801 in humans are expected to begin later this spring. If they are successful, the drug could be used not only to limit the spread of SARS-CoV-2 but also could control future outbreaks of other emerging coronaviruses.
The results of the team’s most recent study were published online Monday by the journal Science Translational Medicine; Baric was listed as a senior author. The paper 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, when used as a prophylactic, EIDD-2801 can prevent severe lung injury in infected mice. EIDD-2801 is an orally available form of the antiviral compound EIDD-1931; it can be taken as a pill and can be properly absorbed to travel to the lungs.
When given as a treatment 12 to 24 hours after infection has begun, EIDD-2801 can reduce the degree of lung damage and weight loss in mice. This window of opportunity is expected to be longer in humans, because the period between coronavirus disease onset and death generally is extended in humans compared to mice.
“This new drug not only has high potential for treating COVID-19 patients but also appears effective for the treatment of other serious coronavirus infections,” Baric said.
Compared with other potential COVID-19 treatments that must be administered intravenously, EIDD-2801 offers ease of treatment and a potential advantage for treating less-ill patients or for prophylaxis — for example, in a nursing home where many people have been exposed but are not yet sick.
“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. This work shows the importance of ongoing National Institutes of Health support for collaborative research to develop antivirals for all pandemic viruses, not just coronaviruses,” said Andrea Pruijssers, the lead antiviral scientist in the Denison Lab at VUMC.
Denison was senior author of a December 2019 study that first reported that EIDD-1931 blocked the replication of a broad spectrum of coronaviruses.
These interinstitutional 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 new Science Translational Medicine paper, Maria Agostini, a postdoctoral fellow in the Denison lab, demonstrated that viruses that show resistance to remdesivir experience higher inhibition from EIDD-1931.
“Viruses that carry remdesivir resistance mutations are actually more susceptible to EIDD-1931 and vice versa, suggesting that the two drugs could be combined for greater efficacy and to prevent the emergence of resistance,” Painter said.
“With three novel human coronaviruses emerging in the past 20 years, it is likely that we will continue to see more,” said first author Timothy Sheahan ’08 (PhD), a Gillings assistant professor of epidemiology and a collaborator in Baric’s lab. “EIDD-2801 holds promise to not only treat COVID-19 patients today but to treat new coronaviruses that may emerge in the future.”