Experimental Antiviral Drug Proves Dramatically Effective at Preventing and Treating COVID-19

Molnupiravir, an antiviral originally designed to fight the flu, is being developed as a treatment for COVID-19 by Ridgeback Biotherapeutics (Miami, FL, USA) in collaboration with Merck (Kenilworth, NJ, USA). Scientists at the University of North Carolina School of Medicine (Chapel Hill, NC, USA) tested how the orally administered experimental drug halts SARS-CoV-2 replication and prevents infection of human cells in a new in vivo model containing human lung tissue. They found that the drug was extremely effective at preventing and treating SARS-CoV-2 infection. Phase 2 and 3 clinical trials are ongoing to evaluate EIDD-2801 safety in humans and its effect on viral shedding in COVID-19 patients.

Mouse models can be useful in studying highly pathogenic human coronaviruses including SARS-CoV-2 and compounds that might control infection. But human coronaviruses do not replicate in mice unless researchers alter the virus, genetically modify the mice, or introduce the individual human receptor genes into mice so the virus can infect cells. Such mouse models have added to the scientific community’s understanding of coronavirus infection and disease progression, but none of these models possess the diverse human cells found in human lungs where viral infection can cause severe disease. The scientists created a solution to this problem – a line of mice with human lung tissue that includes all the primary human cells infected when individuals fall ill with COVID-19.

Immune-deficient mice implanted with human lung tissue (LoM) allowed for replication of SARS-CoV-2, which resulted in infection that recapitulates several features of early diffuse lung damage seen in COVID-19 patients. In addition, acute SARS-CoV-2 infection induced a robust and sustained Type I interferon and inflammatory cytokine/chemokine response. To evaluate the therapeutic efficacy of EIDD-2801 for COVID-19, the researchers administered EIDD-2801 to LoM starting 24 hours or 48 hours post SARS-CoV-2 exposure and every 12 hours thereafter.

“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,” said senior author J. Victor Garcia, PhD, professor of medicine and director of the International Center for the Advancement of Translational Science. “Virus titers were significantly reduced by 96% when treatment was started 48 hours post-exposure.”

Next, the researchers tested the ability of EIDD-2801 to prevent SARS-CoV-2 infection by administering the drug 12 hours prior to SARS-CoV-2 exposure and every 12 hours thereafter.

“Remarkably, we found that EIDD-2801 pre-exposure prophylaxis significantly inhibited SARS-CoV-2 replication - reducing virus titers in the human lung tissues of LoM by over 100,000 fold in two independent experiments,” said co-first author Angela Wahl, PhD, assistant professor of medicine and assistant director of the International Center for the Advancement of Translational Science.

“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,” said Ralph Baric, PhD, the William Kenan Distinguished Professor of Epidemiology 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 efficacious in treating and preventing COVID-19, it could also prove to be highly effective against future coronavirus outbreaks as well.”


Related Links:
Ridgeback Biotherapeutics
Merck
UNC School of Medicine