Detailed analysis of SARS-CoV-2 showed predominant infection of human lung epithelial cells.
A recent study conducted by investigators from the University of North Carolina (UNC) School of Medicine, in collaboration with the UNC Gilling’s School of Global Public Health, has found that the experimental antiviral EIDD-2801 stopped the replication of the SARS-CoV-2 virus and prevented human cells from becoming infected. Results from the study were published in the journal Nature.
"We show that LoM allow for the in vivo study of all recently emerged human coronaviruses in a single platform," Lisa Gralinski, PhD, co-author on the study said. "Our model allows researchers to directly compare infection between human coronaviruses and the effectiveness of potential preventative and therapeutic approaches."
With cases of the coronavirus disease 2019 (COVID-19) rising across the globe, it is paramount to find therapies that will halt its spread. Although various vaccines have been authorized for emergency use, the levels of vaccination needed will take time, as issues with manufacturing, shipping, storage and distribution are still being sorted out.
The investigators behind the study created human lung tissue models and implanted them in immune-deficient mice, which allowed the virus to replicate and infect them. Early diffuse lung damage caused by the disease presented in the mice similarly as it does in humans. Additionally, the infection induced a robust and sustained type 1 interferon and inflammatory cytokine/chemokine response. They then administered the antiviral therapy to the mice 24 or 48 hours after exposure to SARS-CoV-2, and every 12 hours after.
"We found that EIDD-2801 had a remarkable effect on virus replication after only two days of treatment - a dramatic, more than 25,000-fold reduction in the number of infectious particles in human lung tissue when treatment was initiated 24 hours post-exposure," J. Victor Garcia, senior author and professor of medicine and director of the International Center for the Advancement of Translational Science said. "Virus titers were significantly reduced by 96% when treatment was started 48 hours post-exposure."
Separate phase 2 and 3 trials are currently ongoing to evaluate EIDD-2801 safety in humans, as well as its impact on viral shedding in patients with a confirmed case of COVID-19.
"Previously, we demonstrated that EIDD-2801 is also efficacious against SARS-CoV and MERS-CoV infection in vivo and in primary human airway epithelial cultures," Ralph Baric, the William Kenan Distinguished Professor of Epidemiology at the UNC Gilling’s School of Global Public Health and the UNC School of Medicine said. "Overall, these results indicate that EIDD-2801 may not only be efficacious in treating and preventing COVID-19, it could also prove to be highly effective against future coronavirus outbreaks as well."