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CHAPEL HILL – An investigational drug created at a subsidiary of Emory University has shown potential to prevent and treat COVID-19, according to researchers at UNC-Chapel Hill.
The drug, known as EIDD-2801, is being developed by Miami-based Ridgeback Biotherapeutics. Ridgeback is partnering with pharmaceutical giant Merck in the development process. The drug was invented at Drug Innovations at Emory, a nonprofit biotech company 100% owned by Emory University, according to Ridgeback.
Publish their work in Nature, scientists from the UNC School of Medicine and the UNC Gillings School of Global Public Health tested how the orally administered investigational drug stops SARS-CoV-2 replication and prevents infection of human cells in a new in vivo [in a living organism] model containing human lung tissue.
They found the drug to be extremely effective in preventing and treating SARS-CoV-2 infection. Phase 2 and 3 clinical trials are underway to assess the safety of EIDD-2801 in humans and its effect on viral shedding – when a virus replicates inside your body and is released into the environment – in patients with COVID-19.
UNC scientists have created a solution to the problem of mouse models in which coronaviruses do not replicate by creating a mouse line with human lung tissue that includes all of the primary human cells infected when individuals fall ill with COVID -19.
“We found that EIDD-2801 had a remarkable effect on virus replication after just two days of treatment – a dramatic reduction, over 25,000 times, in the number of infectious particles in human lung tissue when treatment was launched 24 hours after exposure, ”said lead author J. Victor Garcia, PhD, professor of medicine and director of the International Center for the Advancement of Translational Science. “Viral titers were significantly reduced by 96% when treatment was started 48 hours after exposure.”
Next, the researchers tested the ability of EIDD-2801 to prevent infection with SARS-CoV-2 by administering the drug 12 hours before exposure to SARS-CoV-2 and every 12 hours thereafter. .
“Remarkably, we found that EIDD-2801 pre-exposure prophylaxis significantly inhibited SARS-CoV-2 replication – reducing viral titers in human lung tissue of LoM by more than 100,000-fold in two independent experiments, ”said co-first author Angela Wahl, PhD, assistant professor of medicine and deputy director of the International Center for the Advancement of Translational Sciences.
Bats are the suspected source of SARS-CoV-2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV, which have all appeared in the human population over the past two decades.
“We show that the LoM allows the in vivo study of all recently appeared human coronaviruses on a single platform, ”said co-first author Lisa Gralinski, PhD, assistant professor of epidemiology. “Our model allows researchers to directly compare the infection between human coronaviruses and the effectiveness of potential preventive and therapeutic approaches.”
Gralinski, added: “We also show efficient replication of endogenous bat coronaviruses in human lung tissue LoM without the need for prior virus adaptation, confirming that bats harbor viruses capable of directly infecting humans without the need for further adaptation.
“Previously, we have demonstrated that EIDD-2801 is also effective against SARS-CoV and MERS-CoV infections in vivo and in epithelial cultures of the primary human respiratory tract,” said Ralph Baric, PhD, professor. Distinguished Epidemiologist William Kenan at the UNC Gillings School of Global Public Health and the UNC School of Medicine. “Overall, these results indicate that EIDD-2801 may not only be effective in treating and preventing COVID-19, but it could also prove to be very effective against future coronavirus outbreaks.”
The other authors are Claire Johnson, Wenbo Yao, Martina Kovarova, Kenneth Dinnon III, Hongwei Liu, Victoria Madden, Halina Krzystek, Chandrav De, Kristen White, Kendra Gully, Alexandra Schäfer, Tanzila Zaman, Sarah Leist, Paul Grant, Frederic Askin, Edward Browne, Corbin Jones and Raymond Pickles, all from UNC-Chapel Hill, and Gregory Bluemling, Alexander Kolykhaloy, Michael Natchus, George Painter from Emory University.
This work was supported by grants from the National Institutes of Health and the North Carolina Coronavirus Relief Fund.
(C) UNC-CH with content provided by WRAL TechWire
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